Journal of Developmental Biology

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16 pages, 2518 KiB

Open AccessArticle

Methyl-Beta-Cyclodextrin Restores Aberrant Bone Morphogenetic Protein 2-Signaling in Bone Marrow Stromal Cells Obtained from Aged C57BL/6 Mice

by Daniel Halloran, Venu Pandit, Kelechi Chukwuocha and Anja Nohe

J. Dev. Biol. 2024, 12(4), 30; https://doi.org/10.3390/jdb12040030 - 18 Nov 2024

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Abstract

During aging, disruptions in various signaling pathways become more common. Some older patients will exhibit irregular bone morphogenetic protein (BMP) signaling, which can lead to osteoporosis (OP)—a debilitating bone disease resulting from an imbalance between osteoblasts and osteoclasts. In 2002, the Food and [...] Read more.

During aging, disruptions in various signaling pathways become more common. Some older patients will exhibit irregular bone morphogenetic protein (BMP) signaling, which can lead to osteoporosis (OP)—a debilitating bone disease resulting from an imbalance between osteoblasts and osteoclasts. In 2002, the Food and Drug Administration (FDA) approved recombinant human BMP-2 (rhBMP-2) for use in spinal fusion surgeries as it is required for bone formation. However, complications with rhBMP-2 arose and primary osteoblasts from OP patients often fail to respond to BMP-2. Although patient samples are available for study, previous medical histories can impact results. Consequently, the C57BL/6 mouse line serves as a valuable model for studying OP and aging. We find that BMP receptor type Ia (BMPRIa) is upregulated in the bone marrow stromal cells (BMSCs) of 15-month-old mice, consistent with prior data. Furthermore, conjugating BMP-2 with Quantum Dots (QDot^®s) allows effective binding to BMPRIa, creating a fluorescent tag for BMP-2. Furthermore, after treating BMSCs with methyl-β-cyclodextrin (MβCD), a disruptor of cellular endocytosis, BMP signaling is restored in 15-month-old mice, as shown by von Kossa assays. MβCD has the potential to restore BMPRIa function, and the BMP signaling pathway offers a promising avenue for future OP therapies. Full article

(This article belongs to the Special Issue The 10th Anniversary of JDB: Feature Papers)

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16 pages, 2085 KiB

Open AccessArticle

Evolution and Spatiotemporal Expression of ankha and ankhb in Zebrafish

by Nuwanthika Wathuliyadde, Katherine E. Willmore and Gregory M. Kelly

J. Dev. Biol. 2024, 12(3), 23; https://doi.org/10.3390/jdb12030023 - 9 Sep 2024

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Abstract

Craniometaphyseal Dysplasia (CMD) is a rare skeletal disorder that can result from mutations in the ANKH gene. This gene encodes progressive anksylosis (ANK), which is responsible for transporting inorganic pyrophosphate (PPi) and ATP from the intracellular to the extracellular environment, where PPi inhibits [...] Read more.

Craniometaphyseal Dysplasia (CMD) is a rare skeletal disorder that can result from mutations in the ANKH gene. This gene encodes progressive anksylosis (ANK), which is responsible for transporting inorganic pyrophosphate (PPi) and ATP from the intracellular to the extracellular environment, where PPi inhibits bone mineralization. When ANK is dysfunctional, as in patients with CMD, the passage of PPi to the extracellular environment is reduced, leading to excess mineralization, particularly in bones of the skull. Zebrafish may serve as a promising model to study the mechanistic basis of CMD. Here, we provide a detailed analysis of the zebrafish Ankh paralogs, Ankha and Ankhb, in terms of their phylogenic relationship with ANK in other vertebrates as well as their spatiotemporal expression patterns during zebrafish development. We found that a closer evolutionary relationship exists between the zebrafish Ankhb protein and its human and other vertebrate counterparts, and stronger promoter activity was predicted for ankhb compared to ankha. Furthermore, we noted distinct temporal expression patterns, with ankha more prominently expressed in early development stages, and both paralogs also being expressed at larval growth stages. Whole-mount in situ hybridization was used to compare the spatial expression patterns of each paralog during bone development, and both showed strong expression in the craniofacial region as well as the notochord and somites. Given the substantial overlap in spatiotemporal expression but only subtle patterning differences, the exact roles of these genes remain speculative. In silico analyses predicted that Ankha and Ankhb have the same function in transporting PPi across the membrane. Nevertheless, this study lays the groundwork for functional analyses of each ankh paralog and highlights the potential of using zebrafish to find possible targeted therapies for CMD. Full article

(This article belongs to the Special Issue The 10th Anniversary of JDB: Feature Papers)

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16 pages, 16966 KiB

Open AccessArticle

Harderian Gland Development and Degeneration in the Fgf10-Deficient Heterozygous Mouse

by Shiori Ikeda, Keita Sato, Hirofumi Fujita, Hitomi Ono-Minagi, Satoru Miyaishi, Tsutomu Nohno and Hideyo Ohuchi

J. Dev. Biol. 2024, 12(2), 16; https://doi.org/10.3390/jdb12020016 - 3 Jun 2024

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Abstract

The mouse Harderian gland (HG) is a secretory gland that covers the posterior portion of the eyeball, opening at the base of the nictitating membrane. The HG serves to protect the eye surface from infection with its secretions. Mice open their eyelids at [...] Read more.

The mouse Harderian gland (HG) is a secretory gland that covers the posterior portion of the eyeball, opening at the base of the nictitating membrane. The HG serves to protect the eye surface from infection with its secretions. Mice open their eyelids at about 2 weeks of age, and the development of the HG primordium mechanically opens the eye by pushing the eyeball from its rear. Therefore, when HG formation is disturbed, the eye exhibits enophthalmos (the slit-eye phenotype), and a line of Fgf10^+/− heterozygous loss-of-function mice exhibits slit-eye due to the HG atrophy. However, it has not been clarified how and when HGs degenerate and atrophy in Fgf10^+/− mice. In this study, we observed the HGs in embryonic (E13.5 to E19), postnatal (P0.5 to P18) and 74-week-old Fgf10^+/− mice. We found that more than half of the Fgf10^+/− mice had markedly degenerated HGs, often unilaterally. The degenerated HG tissue had a melanized appearance and was replaced by connective tissue, which was observed by P10. The development of HGs was delayed or disrupted in the similar proportion of Fgf10^+/− embryos, as revealed via histology and the loss of HG-marker expression. In situ hybridization showed Fgf10 expression was observed in the Harderian mesenchyme in wild-type as well as in the HG-lacking heterozygote at E19. These results show that the Fgf10 haploinsufficiency causes delayed or defective HG development, often unilaterally from the unexpectedly early neonatal period. Full article

(This article belongs to the Special Issue The 10th Anniversary of JDB: Feature Papers)

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19 pages, 3296 KiB

Open AccessArticle

A Residual N-Terminal Peptide Enhances Signaling of Depalmitoylated Hedgehog to the Patched Receptor

by Sophia F. Ehlers, Dominique Manikowski, Georg Steffes, Kristina Ehring, Fabian Gude and Kay Grobe

J. Dev. Biol. 2024, 12(2), 11; https://doi.org/10.3390/jdb12020011 - 9 Apr 2024

Viewed by 1764

Abstract

During their biosynthesis, Sonic hedgehog (Shh) morphogens are covalently modified by cholesterol at the C-terminus and palmitate at the N-terminus. Although both lipids initially anchor Shh to the plasma membrane of producing cells, it later translocates to the extracellular compartment to direct developmental [...] Read more.

During their biosynthesis, Sonic hedgehog (Shh) morphogens are covalently modified by cholesterol at the C-terminus and palmitate at the N-terminus. Although both lipids initially anchor Shh to the plasma membrane of producing cells, it later translocates to the extracellular compartment to direct developmental fates in cells expressing the Patched (Ptch) receptor. Possible release mechanisms for dually lipidated Hh/Shh into the extracellular compartment are currently under intense debate. In this paper, we describe the serum-dependent conversion of the dually lipidated cellular precursor into a soluble cholesteroylated variant (Shh^C) during its release. Although Shh^C is formed in a Dispatched- and Scube2-dependent manner, suggesting the physiological relevance of the protein, the depalmitoylation of Shh^C during release is inconsistent with the previously postulated function of N-palmitate in Ptch receptor binding and signaling. Therefore, we analyzed the potency of Shh^C to induce Ptch-controlled target cell transcription and differentiation in Hh-sensitive reporter cells and in the Drosophila eye. In both experimental systems, we found that Shh^C was highly bioactive despite the absence of the N-palmitate. We also found that the artificial removal of N-terminal peptides longer than eight amino acids inactivated the depalmitoylated soluble proteins in vitro and in the developing Drosophila eye. These results demonstrate that N-depalmitoylated Shh^C requires an N-peptide of a defined minimum length for its signaling function to Ptch. Full article

(This article belongs to the Special Issue The 10th Anniversary of JDB: Feature Papers)

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10 pages, 1434 KiB

Open AccessArticle

Effect of Cyclic Adenosine Monophosphate on Connexin 37 Expression in Sheep Cumulus-Oocyte Complexes

by Mengyao Zhao, Gerile Subudeng, Yufen Zhao, Shaoyu Hao and Haijun Li

J. Dev. Biol. 2024, 12(2), 10; https://doi.org/10.3390/jdb12020010 - 27 Mar 2024

Viewed by 1801

Abstract

Gap junctional connection (GJC) in the cumulus–oocyte complex (COC) provides necessary support for message communication and nutrient transmission required for mammalian oocyte maturation. Cyclic adenosine monophosphate (cAMP) is not only a prerequisite for regulating oocyte meiosis, but also the key intercellular factor for [...] Read more.

Gap junctional connection (GJC) in the cumulus–oocyte complex (COC) provides necessary support for message communication and nutrient transmission required for mammalian oocyte maturation. Cyclic adenosine monophosphate (cAMP) is not only a prerequisite for regulating oocyte meiosis, but also the key intercellular factor for affecting GJC function in COCs. However, there are no reports on whether cAMP regulates connexin 37 (Cx37) expression, one of the main connexin proteins, in sheep COCs. In this study, the expression of Cx37 protein and gene in immature sheep COC was detected using immunohistochemistry and PCR. Subsequently, the effect of cAMP on Cx37 expression in sheep COCs cultured in a gonadotropin-free culture system for 10 min or 60 min was evaluated using competitive ELISA, real-time fluorescent quantitative PCR (RT-qPCR), and Western blot. The results showed that the Cx37 protein was present in sheep oocytes and cumulus cells; the same results were found with respect to GJA4 gene expression. In the gonadotropin-free culture system, compared to the control, significantly higher levels of cAMP as well as Cx37 gene and protein expression were found in sheep COCs following treatment in vitro with Forskolin and IBMX (100 μM and 500 μM)) for 10 min (p < 0.05). Compared to the controls (at 10 or 60 min), cAMP levels in sheep COCs were significantly elevated as a result of Forskolin and IBMX treatment (p < 0.05). Following culturing in vitro for 10 min or 60 min, Forskolin and IBMX treatment can significantly promote Cx37 expression in sheep COCs (p < 0.05), a phenomenon which can be counteracted when the culture media is supplemented with RP-cAMP, a cAMP-specific competitive inhibitor operating through suppression of the protein kinase A (PKA). In summary, this study reports the preliminary regulatory mechanism of cAMP involved in Cx37 expression for the first time, and provides a novel explanation for the interaction between cAMP and GJC communication during sheep COC culturing in vitro. Full article

(This article belongs to the Special Issue The 10th Anniversary of JDB: Feature Papers)

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11 pages, 2738 KiB

Open AccessArticle

Developmental Anomalies in Human Teeth: Odontoblastic Differentiation in Hamartomatous Calcifying Hyperplastic Dental Follicles Presenting with DSP, Nestin, and HES1

by Hiromasa Hasegawa, Katsumitsu Shimada, Takanaga Ochiai and Yasuo Okada

J. Dev. Biol. 2024, 12(1), 7; https://doi.org/10.3390/jdb12010007 - 30 Jan 2024

Cited by 1 | Viewed by 2065

Abstract

Hyperplastic dental follicles (HDFs) represent odontogenic hamartomatous lesions originating from the pericoronal tissues and are often associated with impacted or embedded teeth. These lesions may occasionally feature unique calcifying bodies, known as calcifying whorled nodules (CWNs), characterized by stromal cells arranged in a [...] Read more.

Hyperplastic dental follicles (HDFs) represent odontogenic hamartomatous lesions originating from the pericoronal tissues and are often associated with impacted or embedded teeth. These lesions may occasionally feature unique calcifying bodies, known as calcifying whorled nodules (CWNs), characterized by stromal cells arranged in a whorled or spiral fashion. CWNs are typically observed in multiple calcifying hyperplastic dental follicles or regional odontodysplasia. In our study, we examined 40 cases of HDFs, including nine instances with characteristics of CWNs, referred to as calcifying hyperplastic dental follicles (CHDFs), which are infrequently accompanied by odontodysplasia. The median ages of the HDFs and CHDFs were 16 (ranging from 3 to 66) and 15 (ranging from 11 to 50) years, respectively. The lower third molars were the most frequently affected by HDSFs and CHDFs, followed by the upper canines. A histological examination was conducted on all 40 cases, with an immunohistochemical analysis performed on 21 of them. Among the cases with CWN, nine affected a single embedded tooth, with one exception. CWNs exhibited diverse calcifications featuring sparse or entirely deposited psammoma bodies, and some displayed dentinoid formation. Immunohistochemically, the stromal cells of HDFs were frequently positive for CD56 and nestin. By contrast, CWNs were negative for CD56 but positive for nestin as well as hairy and enhancer split 1 (HES1), with a few dentin sialoprotein (DSP)-positive calcified bodies. Our results revealed that hamartomatous CHDFs can impact multiple and single-embedded teeth. CWNs composed of nestin and HES1-positive ectomesenchymal cells demonstrated the potential to differentiate into odontoblasts and contribute to dentin matrix formation under the influence of HES1. This study is the first report documenting odontoblastic differentiation in HDFs. The rare occurrence of HDFs and CHDFs contributes to limited comprehension. To prevent misdiagnosis, a better understanding of these conditions is necessary. Full article

(This article belongs to the Special Issue The 10th Anniversary of JDB: Feature Papers)

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13 pages, 9070 KiB

Open AccessArticle

Identification of a Chondrocyte-Specific Enhancer in the Hoxc8 Gene

by Stephania A. Cormier and Claudia Kappen

J. Dev. Biol. 2024, 12(1), 5; https://doi.org/10.3390/jdb12010005 - 24 Jan 2024

Viewed by 1966

Abstract

Hox genes encode transcription factors whose roles in patterning animal body plans during embryonic development are well-documented. Multiple studies demonstrate that Hox genes continue to act in adult cells, in normal differentiation, in regenerative processes, and, with abnormal expression, in diverse types of [...] Read more.

Hox genes encode transcription factors whose roles in patterning animal body plans during embryonic development are well-documented. Multiple studies demonstrate that Hox genes continue to act in adult cells, in normal differentiation, in regenerative processes, and, with abnormal expression, in diverse types of cancers. However, surprisingly little is known about the regulatory mechanisms that govern Hox gene expression in specific cell types, as they differentiate during late embryonic development, and in the adult organism. The murine Hoxc8 gene determines the identity of multiple skeletal elements in the lower thoracic and lumbar region and continues to play a role in the proliferation and differentiation of cells in cartilage as the skeleton matures. This study was undertaken to identify regulatory elements in the Hoxc8 gene that control transcriptional activity, specifically in cartilage-producing chondrocytes. We report that an enhancer comprising two 416 and 224 bps long interacting DNA elements produces reporter gene activity when assayed on a heterologous transcriptional promoter in transgenic mice. This enhancer is distinct in spatial, temporal, and molecular regulation from previously identified regulatory sequences in the Hoxc8 gene that control its expression in early development. The identification of a tissue-specific Hox gene regulatory element now allows mechanistic investigations into Hox transcription factor expression and function in differentiating cell types and adult tissues and to specifically target these cells during repair processes and regeneration. Full article

(This article belongs to the Special Issue The 10th Anniversary of JDB: Feature Papers)

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12 pages, 29836 KiB

Open AccessFeature PaperArticle

Cytology Techniques Can Provide Insight into Human Placental Structure Including Syncytiotrophoblast Nuclear Spatial Organisation

by Cassie Fives, André Toulouse, Louise Kenny, Therese Brosnan, Julie McCarthy and Brendan Fitzgerald

J. Dev. Biol. 2023, 11(4), 46; https://doi.org/10.3390/jdb11040046 - 15 Dec 2023

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Abstract

The aim of this study was to provide the first systematic description of human placental cytology appearances and to investigate syncytiotrophoblast nuclear organisation patterns using cytology techniques. Term placentas from normal pregnancies were sampled using fine-needle aspiration (FNA) and direct scrapes. Standard histological [...] Read more.

The aim of this study was to provide the first systematic description of human placental cytology appearances and to investigate syncytiotrophoblast nuclear organisation patterns using cytology techniques. Term placentas from normal pregnancies were sampled using fine-needle aspiration (FNA) and direct scrapes. Standard histological examination was also performed to exclude pathological changes in the placentas being studied. Both Papanicolaou-stained cytospin preparations and air-dried Giemsa slides from FNA provided high-quality material for cytological assessment with good cellularity. Among the key features of the cytology preparations were villous “microbiopsies” that allowed for the three-dimensional appreciation of villous branching patterns. Cytological appearances, including nuclear characteristics of villous cytotrophoblast and syncytiotrophoblast, were also well demonstrated. In microbiopsies and detached villous trophoblast sheets, complex patterns of syncytiotrophoblast nuclear organisation, not previously described cytologically, were observed, including irregular spacing of nuclei, syncytioplasm windows and linear nuclear arrangements. This study showed that placental cytology (a) provides technically excellent material for cytological evaluation, (b) confirms the presence of complex nuclear organisational patterns in the syncytiotrophoblast by eliminating the possibility of tangential sectioning artefact, (c) provides superior nuclear detail over standard histological sections and (d) may be an untapped research resource for the investigation of normal and pathological processes because of its ability to look at the placenta in a novel way and through its potential for both ex vivo and in vivo placental sampling. Full article

(This article belongs to the Special Issue The 10th Anniversary of JDB: Feature Papers)

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28 pages, 38808 KiB

Open AccessArticle

Special Nuclear Structures in the Germinal Vesicle of the Common Frog with Emphasis on the So-Called Karyosphere Capsule

by Dmitry S. Bogolyubov, Sergey V. Shabelnikov, Alexandra O. Travina, Maksim I. Sulatsky and Irina O. Bogolyubova

J. Dev. Biol. 2023, 11(4), 44; https://doi.org/10.3390/jdb11040044 - 12 Dec 2023

Viewed by 2062

Abstract

The karyosphere (karyosome) is a structure that forms in the oocyte nucleus—germinal vesicle (GV)—at the diplotene stage of meiotic prophase due to the assembly of all chromosomes in a limited portion of the GV. In some organisms, the karyosphere has an extrachromosomal external [...] Read more.

The karyosphere (karyosome) is a structure that forms in the oocyte nucleus—germinal vesicle (GV)—at the diplotene stage of meiotic prophase due to the assembly of all chromosomes in a limited portion of the GV. In some organisms, the karyosphere has an extrachromosomal external capsule, the marker protein of which is nuclear F-actin. Despite many years of theories about the formation of the karyosphere capsule (KC) in the GV of the common frog Rana temporaria, we present data that cast doubt on its existence, at least in this species. Specific extrachromosomal strands, which had been considered the main elements of the frog’s KC, do not form a continuous layer around the karyosphere and, according to immunogold labeling, do not contain structural proteins, such as actin and lamin B. At the same time, F-actin is indeed noticeably concentrated around the karyosphere, creating the illusion of a capsule at the light microscopy/fluorescence level. The barrier-to-autointegration factor (BAF) and one of its functional partners—LEMD2, an inner nuclear membrane protein—are not localized in the strands, suggesting that the strands are not functional counterparts of the nuclear envelope. The presence of characteristic strands in the GV of R. temporaria late oocytes may reflect an excess of SMC1 involved in the structural maintenance of diplotene oocyte chromosomes at the karyosphere stage, since SMC1 has been shown to be the most abundant protein in the strands. Other characteristic microstructures—the so-called annuli, very similar in ultrastructure to the nuclear pore complexes—do not contain nucleoporins Nup35 and Nup93, and, therefore, they cannot be considered autonomous pore complexes, as previously thought. Taken together, our data indicate that traditional ideas about the existence of the R. temporaria KC as a special structural compartment of the GV are to be revisited. Full article

(This article belongs to the Special Issue The 10th Anniversary of JDB: Feature Papers)

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13 pages, 2697 KiB

Open AccessFeature PaperArticle

Regulation and Function of FOXC1 in Osteoblasts

by Sarocha Suthon, Jianjian Lin, Rachel S. Perkins, Gustavo A. Miranda-Carboni and Susan A. Krum

J. Dev. Biol. 2023, 11(3), 38; https://doi.org/10.3390/jdb11030038 - 19 Sep 2023

Viewed by 2958

Abstract

Estrogens, which bind to estrogen receptor alpha (ERα), are important for proper bone mineral density. When women go through menopause, estrogen levels decrease, and there is a decrease in bone quality, along with an increased risk for fractures. We previously identified an enhancer [...] Read more.

Estrogens, which bind to estrogen receptor alpha (ERα), are important for proper bone mineral density. When women go through menopause, estrogen levels decrease, and there is a decrease in bone quality, along with an increased risk for fractures. We previously identified an enhancer near FOXC1 as the most significantly enriched binding site for estrogen receptor alpha (ERα) in osteoblasts. FOXC1 is a transcription factor belonging to a large group of proteins known as forkhead box genes and is an important regulator of bone formation. Here, we demonstrate that 17β-estradiol (E2) increases the mRNA and protein levels of FOXC1 in primary mouse and human osteoblasts. GATA4 is a pioneer factor for ERα and it is also recruited to enhancers near Foxc1. Knockdown of Gata4 in mouse osteoblasts in vitro decreases Foxc1 expression as does knockout of Gata4 in vivo. Functionally, GATA4 and FOXC1 interact and regulate osteoblast proteins such as RUNX2, as demonstrated by ChIP-reChIP and luciferase assays. The most enriched motif in GATA4 binding sites from ChIP-seq is for FOXC1, supporting the notion that GATA4 and FOXC1 cooperate in regulating osteoblast differentiation. Together, these data demonstrate the interactions of the transcription factors ERα, GATA4, and FOXC1 to regulate each other’s expression and other osteoblast differentiation genes. Full article

(This article belongs to the Special Issue The 10th Anniversary of JDB: Feature Papers)

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20 pages, 9846 KiB

Open AccessArticle

Vasa, Piwi, and Pl10 Expression during Sexual Maturation and Asexual Reproduction in the Annelid Pristina longiseta

by Roman P. Kostyuchenko and Natalia P. Smirnova

J. Dev. Biol. 2023, 11(3), 34; https://doi.org/10.3390/jdb11030034 - 9 Aug 2023

Cited by 6 | Viewed by 2599

Abstract

Naidids are tiny, transparent freshwater oligochaetes, which are well known for their ability to propagate asexually. Despite the fact that sexually mature individuals and cocoons with embryos are sometimes found in nature, in long-period laboratory cultures, worms reproduce agametically only. In this paper, [...] Read more.

Naidids are tiny, transparent freshwater oligochaetes, which are well known for their ability to propagate asexually. Despite the fact that sexually mature individuals and cocoons with embryos are sometimes found in nature, in long-period laboratory cultures, worms reproduce agametically only. In this paper, we showed, for the first time, the expression of Vasa, Piwi, and Pl10 homologs in mature Pristina longiseta worms with well-developed reproductive system structures and germ cells. Although the animals have been propagated asexually by paratomic fission for over 20 years in our lab, some individuals become sexualized under standard conditions for our laboratory culture and demonstrate various stages of maturation. The fully matured animals developed a complete set of sexual apparatus including spermatheca, atrium, seminal vesicles, and ovisac. They also had a clitellum and were able to form cocoons. The cues for the initiation of sexual maturation are still unknown for P. longiseta; nevertheless, our data suggest that the laboratory strain of P. longiseta maintains the ability to become fully sexually mature and to establish germline products even after a long period of agametic reproduction. On the other hand, many of the sexualized worms formed a fission zone and continued to reproduce asexually. Thus, in this species, the processes of asexual reproduction and sexual maturation do not preclude each other, and Vasa, Piwi, and Pl10 homologs are expressed in both somatic and germline tissue including the posterior growth zone, fission zone, nervous system, germline cells, and gametes. Full article

(This article belongs to the Special Issue The 10th Anniversary of JDB: Feature Papers)

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22 pages, 16646 KiB

Open AccessFeature PaperArticle

Jak2 and Jaw Muscles Are Required for Buccopharyngeal Membrane Perforation during Mouth Development

by Amanda J. G. Dickinson

J. Dev. Biol. 2023, 11(2), 24; https://doi.org/10.3390/jdb11020024 - 31 May 2023

Cited by 1 | Viewed by 2283

Abstract

The mouth is a central feature of our face, without which we could not eat, breathe, or communicate. A critical and early event in mouth formation is the creation of a “hole” which connects the digestive system and the external environment. This hole, [...] Read more.

The mouth is a central feature of our face, without which we could not eat, breathe, or communicate. A critical and early event in mouth formation is the creation of a “hole” which connects the digestive system and the external environment. This hole, which has also been called the primary or embryonic mouth in vertebrates, is initially covered by a 1–2 cell layer thick structure called the buccopharyngeal membrane. When the buccopharyngeal membrane does not rupture, it impairs early mouth functions and may also lead to further craniofacial malformations. Using a chemical screen in an animal model (Xenopus laevis) and genetic data from humans, we determined that Janus kinase 2 (Jak2) has a role in buccopharyngeal membrane rupture. We have determined that decreased Jak2 function, using antisense morpholinos or a pharmacological antagonist, caused a persistent buccopharyngeal membrane as well as the loss of jaw muscles. Surprisingly, we observed that the jaw muscle compartments were connected to the oral epithelium that is continuous with the buccopharyngeal membrane. Severing such connections resulted in buccopharyngeal membrane buckling and persistence. We also noted puncta accumulation of F-actin, an indicator of tension, in the buccopharyngeal membrane during perforation. Taken together, the data has led us to a hypothesis that muscles are required to exert tension across the buccopharyngeal membrane, and such tension is necessary for its perforation. Full article

(This article belongs to the Special Issue The 10th Anniversary of JDB: Feature Papers)

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14 pages, 2734 KiB

Open AccessArticle

The Presence of Two MyoD Genes in a Subset of Acanthopterygii Fish Is Associated with a Polyserine Insert in MyoD1

by Lewis J. White, Alexander J. Russell, Alastair R. Pizzey, Kanchon K. Dasmahapatra and Mary E. Pownall

J. Dev. Biol. 2023, 11(2), 19; https://doi.org/10.3390/jdb11020019 - 28 Apr 2023

Cited by 1 | Viewed by 2250

Abstract

The MyoD gene was duplicated during the teleost whole genome duplication and, while a second MyoD gene (MyoD2) was subsequently lost from the genomes of some lineages (including zebrafish), many fish lineages (including Alcolapia species) have retained both MyoD paralogues. Here [...] Read more.

The MyoD gene was duplicated during the teleost whole genome duplication and, while a second MyoD gene (MyoD2) was subsequently lost from the genomes of some lineages (including zebrafish), many fish lineages (including Alcolapia species) have retained both MyoD paralogues. Here we reveal the expression patterns of the two MyoD genes in Oreochromis (Alcolapia) alcalica using in situ hybridisation. We report our analysis of MyoD1 and MyoD2 protein sequences from 54 teleost species, and show that O. alcalica, along with some other teleosts, include a polyserine repeat between the amino terminal transactivation domains (TAD) and the cysteine-histidine rich region (H/C) in MyoD1. The evolutionary history of MyoD1 and MyoD2 is compared to the presence of this polyserine region using phylogenetics, and its functional relevance is tested using overexpression in a heterologous system to investigate subcellular localisation, stability, and activity of MyoD proteins that include and do not include the polyserine region. Full article

(This article belongs to the Special Issue The 10th Anniversary of JDB: Feature Papers)

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Review

Jump to: Research, Other

14 pages, 799 KiB

Open AccessReview

Roles of the NR2F Family in the Development, Disease, and Cancer of the Lung

by Jiaxin Yang, Wenjing Sun and Guizhong Cui

J. Dev. Biol. 2024, 12(3), 24; https://doi.org/10.3390/jdb12030024 - 10 Sep 2024

Viewed by 1632

Abstract

The NR2F family, including NR2F1, NR2F2, and NR2F6, belongs to the nuclear receptor superfamily. NR2F family members function as transcription factors and play essential roles in the development of multiple organs or tissues in mammals, including the central nervous system, veins and arteries, [...] Read more.

The NR2F family, including NR2F1, NR2F2, and NR2F6, belongs to the nuclear receptor superfamily. NR2F family members function as transcription factors and play essential roles in the development of multiple organs or tissues in mammals, including the central nervous system, veins and arteries, kidneys, uterus, and vasculature. In the central nervous system, NR2F1/2 coordinate with each other to regulate the development of specific brain subregions or cell types. In addition, NR2F family members are associated with various cancers, such as prostate cancer, breast cancer, and esophageal cancer. Nonetheless, the roles of the NR2F family in the development and diseases of the lung have not been systematically summarized. In this review, we mainly focus on the lung, including recent findings regarding the roles of the NR2F family in development, physiological function, and cancer. Full article

(This article belongs to the Special Issue The 10th Anniversary of JDB: Feature Papers)

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21 pages, 1256 KiB

Open AccessReview

Developmental Impacts of Epigenetics and Metabolism in COVID-19

by Noopur Naik, Mansi Patel and Rwik Sen

J. Dev. Biol. 2024, 12(1), 9; https://doi.org/10.3390/jdb12010009 - 9 Feb 2024

Cited by 1 | Viewed by 3030

Abstract

Developmental biology is intricately regulated by epigenetics and metabolism but the mechanisms are not completely understood. The situation becomes even more complicated during diseases where all three phenomena are dysregulated. A salient example is COVID-19, where the death toll exceeded 6.96 million in [...] Read more.

Developmental biology is intricately regulated by epigenetics and metabolism but the mechanisms are not completely understood. The situation becomes even more complicated during diseases where all three phenomena are dysregulated. A salient example is COVID-19, where the death toll exceeded 6.96 million in 4 years, while the virus continues to mutate into different variants and infect people. Early evidence during the pandemic showed that the host’s immune and inflammatory responses to COVID-19 (like the cytokine storm) impacted the host’s metabolism, causing damage to the host’s organs and overall physiology. The involvement of angiotensin-converting enzyme 2 (ACE2), the pivotal host receptor for the SARS-CoV-2 virus, was identified and linked to epigenetic abnormalities along with other contributing factors. Recently, studies have revealed stronger connections between epigenetics and metabolism in COVID-19 that impact development and accelerate aging. Patients manifest systemic toxicity, immune dysfunction and multi-organ failure. Single-cell multiomics and other state-of-the-art high-throughput studies are only just beginning to demonstrate the extent of dysregulation and damage. As epigenetics and metabolism directly impact development, there is a crucial need for research implementing cutting-edge technology, next-generation sequencing, bioinformatics analysis, the identification of biomarkers and clinical trials to help with prevention and therapeutic interventions against similar threats in the future. Full article

(This article belongs to the Special Issue The 10th Anniversary of JDB: Feature Papers)

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16 pages, 1145 KiB

Open AccessReview

Development-Associated Genes of the Epidermal Differentiation Complex (EDC)

by Karin Brigit Holthaus and Leopold Eckhart

J. Dev. Biol. 2024, 12(1), 4; https://doi.org/10.3390/jdb12010004 - 15 Jan 2024

Cited by 2 | Viewed by 2964

Abstract

The epidermal differentiation complex (EDC) is a cluster of genes that encode protein components of the outermost layers of the epidermis in mammals, reptiles and birds. The development of the stratified epidermis from a single-layered ectoderm involves an embryo-specific superficial cell layer, the [...] Read more.

The epidermal differentiation complex (EDC) is a cluster of genes that encode protein components of the outermost layers of the epidermis in mammals, reptiles and birds. The development of the stratified epidermis from a single-layered ectoderm involves an embryo-specific superficial cell layer, the periderm. An additional layer, the subperiderm, develops in crocodilians and over scutate scales of birds. Here, we review the expression of EDC genes during embryonic development. Several EDC genes are expressed predominantly or exclusively in embryo-specific cell layers, whereas others are confined to the epidermal layers that are maintained in postnatal skin. The S100 fused-type proteins scaffoldin and trichohyalin are expressed in the avian and mammalian periderm, respectively. Scaffoldin forms the so-called periderm granules, which are histological markers of the periderm in birds. Epidermal differentiation cysteine-rich protein (EDCRP) and epidermal differentiation protein containing DPCC motifs (EDDM) are expressed in the avian subperiderm where they are supposed to undergo cross-linking via disulfide bonds. Furthermore, a histidine-rich epidermal differentiation protein and feather-type corneous beta-proteins, also known as beta-keratins, are expressed in the subperiderm. The accumulating evidence for roles of EDC genes in the development of the epidermis has implications on the evolutionary diversification of the skin in amniotes. Full article

(This article belongs to the Special Issue The 10th Anniversary of JDB: Feature Papers)

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13 pages, 1585 KiB

Open AccessReview

Established and Evolving Roles of the Multifunctional Non-POU Domain-Containing Octamer-Binding Protein (NonO) and Splicing Factor Proline- and Glutamine-Rich (SFPQ)

by Danyang Yu, Ching-Jung Huang and Haley O. Tucker

J. Dev. Biol. 2024, 12(1), 3; https://doi.org/10.3390/jdb12010003 - 5 Jan 2024

Cited by 6 | Viewed by 2918

Abstract

It has been more than three decades since the discovery of multifunctional factors, the Non-POU-Domain-Containing Octamer-Binding Protein, NonO, and the Splicing Factor Proline- and Glutamine-Rich, SFPQ. Some of their functions, including their participation in transcriptional and posttranscriptional regulation as well as their contribution [...] Read more.

It has been more than three decades since the discovery of multifunctional factors, the Non-POU-Domain-Containing Octamer-Binding Protein, NonO, and the Splicing Factor Proline- and Glutamine-Rich, SFPQ. Some of their functions, including their participation in transcriptional and posttranscriptional regulation as well as their contribution to paraspeckle subnuclear body organization, have been well documented. In this review, we focus on several other established roles of NonO and SFPQ, including their participation in the cell cycle, nonhomologous end-joining (NHEJ), homologous recombination (HR), telomere stability, childhood birth defects and cancer. In each of these contexts, the absence or malfunction of either or both NonO and SFPQ leads to either genome instability, tumor development or mental impairment. Full article

(This article belongs to the Special Issue The 10th Anniversary of JDB: Feature Papers)

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16 pages, 6321 KiB

Open AccessFeature PaperReview

Phase Separation as a Driver of Stem Cell Organization and Function during Development

by Amalia S. Parra and Christopher A. Johnston

J. Dev. Biol. 2023, 11(4), 45; https://doi.org/10.3390/jdb11040045 - 12 Dec 2023

Viewed by 2675

Abstract

A properly organized subcellular composition is essential to cell function. The canonical organizing principle within eukaryotic cells involves membrane-bound organelles; yet, such structures do not fully explain cellular complexity. Furthermore, discrete non-membrane-bound structures have been known for over a century. Liquid–liquid phase separation [...] Read more.

A properly organized subcellular composition is essential to cell function. The canonical organizing principle within eukaryotic cells involves membrane-bound organelles; yet, such structures do not fully explain cellular complexity. Furthermore, discrete non-membrane-bound structures have been known for over a century. Liquid–liquid phase separation (LLPS) has emerged as a ubiquitous mode of cellular organization without the need for formal lipid membranes, with an ever-expanding and diverse list of cellular functions that appear to be regulated by this process. In comparison to traditional organelles, LLPS can occur across wider spatial and temporal scales and involves more distinct protein and RNA complexes. In this review, we discuss the impacts of LLPS on the organization of stem cells and their function during development. Specifically, the roles of LLPS in developmental signaling pathways, chromatin organization, and gene expression will be detailed, as well as its impacts on essential processes of asymmetric cell division. We will also discuss how the dynamic and regulated nature of LLPS may afford stem cells an adaptable mode of organization throughout the developmental time to control cell fate. Finally, we will discuss how aberrant LLPS in these processes may contribute to developmental defects and disease. Full article

(This article belongs to the Special Issue The 10th Anniversary of JDB: Feature Papers)

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12 pages, 1714 KiB

Open AccessFeature PaperReview

SARS-CoV-2 Infection in Late Pregnancy and Childbirth from the Perspective of Perinatal Pathology

by Larisa Debelenko

J. Dev. Biol. 2023, 11(4), 42; https://doi.org/10.3390/jdb11040042 - 16 Nov 2023

Cited by 1 | Viewed by 2292

Abstract

This review focuses on SARS-CoV-2 infection in placental and fetal tissues. Viremia is rare in infected pregnant women, and the virus is seldom amplified from placental tissues. Definite and probable placental infection requires the demonstration of viral RNA or proteins using in situ [...] Read more.

This review focuses on SARS-CoV-2 infection in placental and fetal tissues. Viremia is rare in infected pregnant women, and the virus is seldom amplified from placental tissues. Definite and probable placental infection requires the demonstration of viral RNA or proteins using in situ hybridization (ISH) and immunohistochemistry (IHC). Small subsets (1.0–7.9%, median 2.8%) of placentas of SARS-CoV-2-positive women showed definite infection accompanied by a characteristic histopathology named SARS-CoV-2 placentitis (SP). The conventionally accepted histopathological criteria for SP include the triad of intervillositis, perivillous fibrin deposition, and trophoblast necrosis. SP was shown to be independent of the clinical severity of the infection, but associated with stillbirth in cases where destructive lesions affecting more than 75% of the placental tissue resulted in placental insufficiency and severe fetal hypoxic–ischemic injury. An association between maternal thrombophilia and SP was shown in a subset of cases, suggesting a synergy of the infection and deficient coagulation cascade as one of the mechanisms of the pathologic accumulation of fibrin in affected placentas. The virus was amplified from fetal tissues in approximately 40% of SP cases, but definite fetal involvement demonstrated using ISH or IHC is exceptionally rare. The placental pathology in SARS-CoV-2-positive women also includes chronic lesions associated with placental malperfusion in the absence of definite or probable placental infection. The direct viral causation of the vascular malperfusion of the placenta in COVID-19 is debatable, and common predispositions (hypertension, diabetes, and obesity) may play a role. Full article

(This article belongs to the Special Issue The 10th Anniversary of JDB: Feature Papers)

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22 pages, 1852 KiB

Open AccessReview

Evolutionary Change in Gut Specification in Caenorhabditis Centers on the GATA Factor ELT-3 in an Example of Developmental System Drift

by Gina Broitman-Maduro and Morris F. Maduro

J. Dev. Biol. 2023, 11(3), 32; https://doi.org/10.3390/jdb11030032 - 8 Jul 2023

Viewed by 1926

Abstract

Cells in a developing animal embryo become specified by the activation of cell-type-specific gene regulatory networks. The network that specifies the gut in the nematode Caenorhabditis elegans has been the subject of study for more than two decades. In this network, the maternal [...] Read more.

Cells in a developing animal embryo become specified by the activation of cell-type-specific gene regulatory networks. The network that specifies the gut in the nematode Caenorhabditis elegans has been the subject of study for more than two decades. In this network, the maternal factors SKN-1/Nrf and POP-1/TCF activate a zygotic GATA factor cascade consisting of the regulators MED-1,2 → END-1,3 → ELT-2,7, leading to the specification of the gut in early embryos. Paradoxically, the MED, END, and ELT-7 regulators are present only in species closely related to C. elegans, raising the question of how the gut can be specified without them. Recent work found that ELT-3, a GATA factor without an endodermal role in C. elegans, acts in a simpler ELT-3 → ELT-2 network to specify gut in more distant species. The simpler ELT-3 → ELT-2 network may thus represent an ancestral pathway. In this review, we describe the elucidation of the gut specification network in C. elegans and related species and propose a model by which the more complex network might have formed. Because the evolution of this network occurred without a change in phenotype, it is an example of the phenomenon of Developmental System Drift. Full article

(This article belongs to the Special Issue The 10th Anniversary of JDB: Feature Papers)

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19 pages, 1292 KiB

Open AccessFeature PaperReview

Genetic and Epigenetic Regulation of Drosophila Oocyte Determination

by Brigite Cabrita and Rui Gonçalo Martinho

J. Dev. Biol. 2023, 11(2), 21; https://doi.org/10.3390/jdb11020021 - 24 May 2023

Cited by 1 | Viewed by 2820

Abstract

Primary oocyte determination occurs in many organisms within a germ line cyst, a multicellular structure composed of interconnected germ cells. However, the structure of the cyst is itself highly diverse, which raises intriguing questions about the benefits of this stereotypical multicellular environment for [...] Read more.

Primary oocyte determination occurs in many organisms within a germ line cyst, a multicellular structure composed of interconnected germ cells. However, the structure of the cyst is itself highly diverse, which raises intriguing questions about the benefits of this stereotypical multicellular environment for female gametogenesis. Drosophila melanogaster is a well-studied model for female gametogenesis, and numerous genes and pathways critical for the determination and differentiation of a viable female gamete have been identified. This review provides an up-to-date overview of Drosophila oocyte determination, with a particular emphasis on the mechanisms that regulate germ line gene expression. Full article

(This article belongs to the Special Issue The 10th Anniversary of JDB: Feature Papers)

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6 pages, 1644 KiB

Open AccessOpinion

Regeneration Abilities among Extant Animals Depend on Their Evolutionary History and Life Cycles

by Lorenzo Alibardi

J. Dev. Biol. 2024, 12(1), 8; https://doi.org/10.3390/jdb12010008 - 9 Feb 2024

Viewed by 2128

Abstract

The present brief manuscript summarizes the main points supporting recently proposed hypotheses explaining the different distributions of regenerative capacity among invertebrates and vertebrates. The new hypotheses are based on the evolution of regeneration from marine animals to the terrestrial animals derived from them. [...] Read more.

The present brief manuscript summarizes the main points supporting recently proposed hypotheses explaining the different distributions of regenerative capacity among invertebrates and vertebrates. The new hypotheses are based on the evolution of regeneration from marine animals to the terrestrial animals derived from them. These speculations suggest that animals that were initially capable of broad regeneration in the sea underwent epigenetic modifications during terrestrial adaptation that determined the loss of their regenerative abilities in sub-aerial conditions. These changes derived from the requirements of life on land that include variable dry and UV-exposed conditions. Terrestrial conditions do not allow for organ regeneration, especially in arthropods and amniotes. Nematodes, the other main metazoan group unable of regeneration, instead evolved eutely (a fixed number of body cells), a process which is incompatible with regeneration. All these changes involved gene loss, modification and new gene interactions within the genomes of terrestrial adapting animals that gave rise to sophisticated invertebrates and vertebrates adapted to living on land but with low cellular plasticity. Full article

(This article belongs to the Special Issue The 10th Anniversary of JDB: Feature Papers)

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