Journal of Developmental Biology

26 pages, 935 KB

Open AccessReview

An Overview of How Epigenetics, MicroRNA-21, and Endocrine Disrupting Compounds Affect Oocyte Maturation and Pre-Implantation Embryo Development

by Monique Nasser, Reem Sabry and Laura A. Favetta

J. Dev. Biol. 2026, 14(2), 28; https://doi.org/10.3390/jdb14020028 - 5 Jun 2026

Abstract

Epigenetic regulation is pivotal in reproductive processes, such as oocyte maturation and pre-implantation embryonic development, and it impacts gene expression without altering DNA sequence through mechanisms including DNA methylation, histone modifications, and non-coding RNAs. Primarily, microRNA-21 is involved in meiotic progression, apoptosis, and [...] Read more.

Epigenetic regulation is pivotal in reproductive processes, such as oocyte maturation and pre-implantation embryonic development, and it impacts gene expression without altering DNA sequence through mechanisms including DNA methylation, histone modifications, and non-coding RNAs. Primarily, microRNA-21 is involved in meiotic progression, apoptosis, and cumulus cell function, which are necessary for oocyte competency. miR-21 dysregulation can lead to improper oocyte maturation and poor embryonic development, ultimately causing developmental defects. During pre-implantation embryonic development, DNA methylation and histone modifications contribute to cellular reprogramming, ensuring proper gene activation and repression. Environmentally, endocrine disruptors affect miR-21 expression, potentially disrupting pathways involved in reproductive health and developmental programming. Overall, this review explores the correlation between epigenetics, miRNA regulation, and environmental factors, emphasizing the intricacies of oocyte maturation and pre-implantation embryonic development. This highlights the need for additional mechanistic and translational research in reproductive epigenetics. Full article

(This article belongs to the Special Issue Genetic and Epigenetic Mechanisms in Gametogenesis and Early Development: Insights from Models, Stem Cells, and Human Disorders)

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54 pages, 1394 KB

Open AccessReview

The Gut Microbiome in Early Ontogeny: Implications for Brain and Immune System Development

by Alejandro Borrego-Ruiz and Juan J. Borrego

J. Dev. Biol. 2026, 14(2), 27; https://doi.org/10.3390/jdb14020027 - 4 Jun 2026

Abstract

The gut microbiome plays a pivotal role in modulating multiple physiological processes from the earliest stages of life. However, the complete scope of its effects during childhood is yet to be fully elucidated, which underscores the importance of enhancing the understanding of this [...] Read more.

The gut microbiome plays a pivotal role in modulating multiple physiological processes from the earliest stages of life. However, the complete scope of its effects during childhood is yet to be fully elucidated, which underscores the importance of enhancing the understanding of this emerging area of research. This narrative review provides an overview of the influence of the gut microbiome in early human ontogeny by examining its role in brain and immune development, as well as its involvement in neurodevelopmental disorders and early-life mental health. The gut microbiome contributes to shaping the development and function of both the brain and the immune system. Its influence appears to be primarily mediated through the synthesis of neurotransmitters and microbial metabolites, as well as through the activation of specific pathways within the hypothalamic–pituitary–adrenal axis. Nevertheless, the exact mechanisms through which the gut microbiome exerts these effects, and the full extent of its impact on neurodevelopmental and immune health, remain incompletely understood and continue to be active areas of research and scientific debate. Ultimately, advances revealing how the gut microbiome shapes early brain and immune system development will create new opportunities for innovative interventions and predictive strategies aimed at transforming pediatric health outcomes. Full article

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12 pages, 6524 KB

Open AccessArticle

Gestational Dynamics of Hofbauer Cells in the Human Placenta: Distribution, Morphology, and Immunophenotype

by Sanja Jovičić, Ivan R Nikolić, Ljiljana Božić, Marko Jović, Dina Kapić and Ranko Škrbić

J. Dev. Biol. 2026, 14(2), 26; https://doi.org/10.3390/jdb14020026 - 2 Jun 2026

Abstract

Background: Hofbauer cells (HBCs) are the only immunocompetent cells within the stroma of chorionic villi and play a key role in immune regulation and placental development throughout gestation. Their phenotype, abundance, and proliferative activity change in accordance with the needs of the fetoplacental [...] Read more.

Background: Hofbauer cells (HBCs) are the only immunocompetent cells within the stroma of chorionic villi and play a key role in immune regulation and placental development throughout gestation. Their phenotype, abundance, and proliferative activity change in accordance with the needs of the fetoplacental unit. Methods: Thirty healthy human placentas across all three trimesters were analyzed. Samples were processed using standard histological protocols and immunohistochemically stained with CD45, CD68, CD86, and Ki-67 markers. Morphometric analysis was performed to determine the following parameters: percentage of HBCs, numerical areal density, and proliferative index. Results: HBCs were immunoreactive for CD45 and CD68, while CD86 immunoreactivity was not observed in any trimester. The proportion of HBCs was highest in the second trimester and lowest in the third. Numerical areal density was highest in the second trimester (22.21 ± 3.86) and lowest in the first (8.27 ± 4.18). The proliferative index was highest in the first trimester (82.45 ± 10.19%), decreased significantly in the second, and was completely absent in the third trimester. Conclusions: During physiological placental development, Hofbauer cells maintain a predominantly non-M1 macrophage phenotype, accompanied by a gradual reduction in proliferative activity. Full article

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22 pages, 6238 KB

Open AccessArticle

Spatiotemporal Profiling Defines the Epithelial and Mesenchymal Transition Window in Embryonic Lung Morphogenesis

by Huiwen Zheng, Jinpei Lin, Hanyi Li, Shijie Hao and Mengnan Cheng

J. Dev. Biol. 2026, 14(2), 25; https://doi.org/10.3390/jdb14020025 - 1 Jun 2026

Abstract

Lung organogenesis is orchestrated by dynamic epithelial–mesenchymal interactions during embryogenesis, yet the gene regulatory programs and signaling dynamics governing these processes in the pseudoglandular stage remain incompletely understood. In this study, we integrated spatial and single-cell transcriptomic data across embryonic developmental stages to [...] Read more.

Lung organogenesis is orchestrated by dynamic epithelial–mesenchymal interactions during embryogenesis, yet the gene regulatory programs and signaling dynamics governing these processes in the pseudoglandular stage remain incompletely understood. In this study, we integrated spatial and single-cell transcriptomic data across embryonic developmental stages to systematically characterize epithelial and mesenchymal dynamics during lung development. To achieve more refined cell types at single-cell resolution in spatial transcriptomic data, we developed a bin-based deconvolution strategy that enabled high-precision cell-type assignment. We subsequently constructed a 3D spatiotemporal landscape of lung development and elucidated the molecular regulatory mechanisms underlying epithelial–mesenchymal maturation during lung morphogenesis. In addition, we analyzed transcription factor module activity, intercellular communication signaling, and predicted downstream target genes, while integrating public GWAS metadata to link developmental programs with lung cancer-related features. We observed pronounced stage-specific functional heterogeneity between the pseudoglandular and late embryonic stages. Notably, E13.5 emerged as a critical transition window, during which progenitor states shifted toward more mature cellular phenotypes. We reconstructed epithelial–mesenchymal interactions and uncovered coordinated rewiring of ligand–receptor signaling and transcriptional networks across developmental stages. Regulatory network analysis further identified temporally coordinated transcription factor modules centered on Tbx3, Tbx5, Gli1, Gata4/5, Foxa1/2, and Cebpa, which collectively orchestrated branching morphogenesis, epithelial patterning, and tissue stabilization. Integration with lung cancer genome-wide association data demonstrated that embryonic lung progenitor states exhibit strong associations with lung cancer-related transcriptional programs, particularly involving epithelial–mesenchymal plasticity and RNA-splicing pathways. Furthermore, TP53/HNRNP-mutant lung adenocarcinomas displayed embryonic-like molecular features associated with cytoskeletal remodeling and progenitor-state reactivation. Together, our study provided a spatiotemporally resolved framework of embryonic lung development and identifies a critical transition window linking lung morphogenesis, regulatory network remodeling, and cancer-associated epithelial plasticity. Full article

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15 pages, 8053 KB

Open AccessArticle

The Association Between the Progressive Motility of Bovine Spermatozoa and the Developmental Morphokinetics of In Vitro-Derived Embryos

by Shir Maizus, Dorit Kalo, Tanya Kogan, Ariel Michaelov and Zvi Roth

J. Dev. Biol. 2026, 14(2), 24; https://doi.org/10.3390/jdb14020024 - 20 May 2026

Abstract

The proportion of spermatozoa with progressive motility is widely used to evaluate the quality of a single ejaculate. However, the cellular and physiological mechanisms underlying this trait remain unclear. The present study examined the association between the progressive motility of bovine spermatozoa, their [...] Read more.

The proportion of spermatozoa with progressive motility is widely used to evaluate the quality of a single ejaculate. However, the cellular and physiological mechanisms underlying this trait remain unclear. The present study examined the association between the progressive motility of bovine spermatozoa, their quality and their fertilization competence in vitro, and subsequently the association with the developmental morphokinetics of the formed embryos. Fresh ejaculates were classified and divided into groups with high (HPM), medium (MPM), or low (LPM) progressive motility. Then, spermatozoa were evaluated for their morphology, plasma membrane integrity, mitochondrial membrane potential, oxidative status, and acrosome integrity. The findings revealed that spermatozoa from HPM ejaculates enhanced motility in association with higher mitochondrial membrane potential relative to the LPM group, suggesting higher metabolic potential. No differences were recorded in fertilization competence among groups; however, the developmental kinetics of the formed embryos, determined by a time-lapse system, differed; embryos derived from HPM spermatozoa cleaved earlier to the two-, three-, and four-cell stages than embryos derived from MPM spermatozoa, suggesting that HPM-derived embryos are of good quality. Our findings suggest that progressive motility is not only a motility characteristic; it also reflects cellular quality of spermatozoa and the formed embryo. Full article

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19 pages, 4143 KB

Open AccessArticle

Expression and Role of Colony Stimulating Factor 1 Receptor During Odontogenesis

by Ashina Nagra, Ling-Yi Chen, Soheil Saeidiborojeni, Jessica M. Rosin and Siddharth R. Vora

J. Dev. Biol. 2026, 14(2), 23; https://doi.org/10.3390/jdb14020023 - 18 May 2026

Abstract

In osteopetrotic mice with homozygous inactivating mutations in the colony stimulating factor 1 (Csf1^op/op) or its receptor (Csf1r^−/−) gene, teeth fail to erupt due to severe reduction in osteoclastogenesis. Dental abnormalities have been described in the unerupted [...] Read more.

In osteopetrotic mice with homozygous inactivating mutations in the colony stimulating factor 1 (Csf1^op/op) or its receptor (Csf1r^−/−) gene, teeth fail to erupt due to severe reduction in osteoclastogenesis. Dental abnormalities have been described in the unerupted teeth of these models, but it remains unclear whether these defects arise from direct roles of CSF1R in odontogenesis or indirectly from impaired bone remodeling associated with failed eruption. Here, we examined the spatiotemporal expression of CSF1R during tooth development and inhibited CSF1R pharmacologically in utero using PLX5622 during early stages of tooth morphogenesis. Teeth and surrounding bone were analyzed at embryonic and postnatal stages using histology and high-resolution micro-computed tomography. Embryonic CSF1R inhibition resulted in reproducible abnormalities in incisor and molar morphology that were evident before and after birth and were associated with loss of normal bone remodeling at the tooth–bone interface. In contrast, postnatal CSF1R inhibition did not affect the structure or continuous growth of adult incisors. Together, these findings demonstrate a temporally restricted, indirect role for CSF1R in odontogenesis that is independent of tooth eruption and associated with remodeling of the bony crypts surrounding developing teeth by CSF1R-dependent cells. Full article

(This article belongs to the Special Issue Mechanisms of Morphogenesis, Degeneration, and Regeneration)

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17 pages, 20426 KB

Open AccessArticle

Functional and Genetic Analyses Unveil the Implication of hoxa4a in Zebrafish Craniofacial Development

by Le Sun, Lu Ping, Fuyu Zhang, Ruzhen Gao, Bo Zhang and Xiaowei Chen

J. Dev. Biol. 2026, 14(2), 22; https://doi.org/10.3390/jdb14020022 - 15 May 2026

Abstract

Microtia–atresia is a rare craniofacial malformation primarily affecting the first and second pharyngeal arches, leading to the deformity of the auricle and atresia of the external ear canal. Its etiology is heterogenous and largely unknown, including both genetic and environmental factors. The HOXA4 [...] Read more.

Microtia–atresia is a rare craniofacial malformation primarily affecting the first and second pharyngeal arches, leading to the deformity of the auricle and atresia of the external ear canal. Its etiology is heterogenous and largely unknown, including both genetic and environmental factors. The HOXA4 gene has been identified as potentially pathogenetic for microtia–atresia in three twin families. A hoxa4a mosaic knockdown zebrafish model was constructed using CRISPR/Cas9. hoxa4a was expressed in the mandible during early development in zebrafish, while the F0 mosaic knockdowns exhibited craniofacial malformations with abnormal chondrocyte morphologies. Specifically, hoxa4a knockdown reduced cranial neural crest cell proliferation while increasing apoptosis, markedly downregulating chondrogenic markers sox9a and col2a1a. Consequently, pharyngeal arch chondrocytes exhibited disorganized arrangement and morphological abnormalities, resulting in mandibular hypoplasia. Our findings provide important insights into the role of hoxa4a in zebrafish mandibular development and the pathology of microtia–atresia caused by HOXA4 gene mutations in humans. Full article

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11 pages, 1848 KB

Open AccessArticle

Torpor-Induced Regulation of Poly(A) Tail Machinery in 13-Lined Ground Squirrel Brown Adipose Tissue

by Saif Rehman, William G. Willmore and Kenneth B. Storey

J. Dev. Biol. 2026, 14(2), 21; https://doi.org/10.3390/jdb14020021 - 14 May 2026

Abstract

The poly(A) tail has long been known to play a central role in mRNA stability, storage, and translational competence, making it a potential key regulator during hypometabolic states. During seasonal torpor, hibernating mammals must frequently enter these hypometabolic states to survive. In this [...] Read more.

The poly(A) tail has long been known to play a central role in mRNA stability, storage, and translational competence, making it a potential key regulator during hypometabolic states. During seasonal torpor, hibernating mammals must frequently enter these hypometabolic states to survive. In this study, we examined protein abundance changes in key enzymes involved in poly(A) tail synthesis, binding, and removal during torpor in the brown adipose tissue of the 13-lined ground squirrel, Ictidomys tridecemlineatus, using immunoblots. BAT during late torpor exhibited significantly reduced abundance of the catalytic cleavage enzyme CPSF73, but increased abundance of poly(A) polymerase PAPOLA. In contrast, poly(A)-binding proteins and major complex subunits of deadenylases, including CCR4-Not, exhibited no significant changes. Furthermore, despite unchanged levels of the translation initiation factor eIF4E, the phosphorylated variant of 4E-BP1, a potent inhibitor of the initiation factor when hypophosphorylated, was significantly reduced during late torpor. Overall, constrained mRNA maturation, preserved transcript stability, and reversible translational inhibition suggest that an important role exists for poly(A) tail regulatory machinery in hypometabolic survival throughout the torpid state. Full article

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Graphical abstract

20 pages, 3330 KB

Open AccessArticle

Adenosine Receptor Functionality and Desensitization Machinery in a Neuronal Cell Model of Angelman Syndrome

by Martina Contestabile, Jacqueline Fátima Martins de Almeida, Chiara De Cesari, Ilaria Tonazzini, Paolo Giovanni Artini and Simona Daniele

J. Dev. Biol. 2026, 14(2), 20; https://doi.org/10.3390/jdb14020020 - 2 May 2026

Abstract

Angelman syndrome (AS) is a neurodevelopmental disorder caused by the loss of maternal UBE3A expression, leading to disrupted proteostasis and synaptic dysfunction. Adenosine is a ubiquitous neuromodulator whose G protein-coupled receptors (ARs) regulate neuronal differentiation and neurite outgrowth during development. Here, we investigated [...] Read more.

Angelman syndrome (AS) is a neurodevelopmental disorder caused by the loss of maternal UBE3A expression, leading to disrupted proteostasis and synaptic dysfunction. Adenosine is a ubiquitous neuromodulator whose G protein-coupled receptors (ARs) regulate neuronal differentiation and neurite outgrowth during development. Here, we investigated AR signaling and their influence on survival–autophagy balance and neuronal morphology in an AS cellular model. Using SH-SY5Y cells with silenced UBE3A, we found that UBE3A loss markedly decreased A1AR, A2BAR, and A3AR protein levels while significantly increasing A2AR expression. Ligand affinity was preserved across genotypes, but A1AR and A2AAR desensitization kinetics were significantly slower in UBE3A-deficient cells. These effects were associated with reduced recruitment of G protein-coupled receptor kinase 2 (GRK2) to the plasma membrane and decreased GRK2–AR association in UBE3A-deficient cells, suggesting a possible contribution of altered GRK2 dynamics to prolonged AR signaling. Functionally, A1AR and A2AR agonists preferentially promoted survival of UBE3A-deficient cells and modulated the MDM2–p53 axis and autophagy markers; A1R stimulation also increased neurite density in UBE3A-deficient cells. Together, these results identify AR-level alterations and defective desensitization machinery in AS neuronal cells and link receptor changes to downstream proteostasis and morphological phenotypes relevant to AS pathophysiology. Full article

(This article belongs to the Special Issue Molecular and Cellular Mechanisms of Brain Development and Neurodevelopmental Disorders)

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11 pages, 1432 KB

Open AccessReview

Fetal–Fetal and Fetal–Maternal Microchimerism: Insights from Mammalian Placental Biology

by Jorge A. De los Santos Funes

J. Dev. Biol. 2026, 14(2), 19; https://doi.org/10.3390/jdb14020019 - 28 Apr 2026

Abstract

Feto-maternal microchimerism (Mc) refers to the exchange of cells between the fetus and mother, and fetal–fetal Mc to the exchange between fetuses during pregnancy. This phenomenon occurs across mammalian species, including humans, mice, and cattle. Key data on Mc cells and theoretical considerations [...] Read more.

Feto-maternal microchimerism (Mc) refers to the exchange of cells between the fetus and mother, and fetal–fetal Mc to the exchange between fetuses during pregnancy. This phenomenon occurs across mammalian species, including humans, mice, and cattle. Key data on Mc cells and theoretical considerations regarding the presence of fetal-derived material, such as trophoblast cells, cell-free fetal DNA (cffDNA), and exosomes in maternal blood are summarized. This review aims to first, synthesize current knowledge on feto-maternal and fetal–fetal Mc across mammals, second, address three core questions: how and where Mc has been demonstrated in animals, what techniques have been used over time to detect fetal-derived material and Mc, and how placental structures influence the frequency of Mc. Finally, it aims to identify gaps in the literature for species such as horses, goats, and pigs. This article concludes that Mc is a widespread phenomenon among mammals, but detection methods and reported frequencies vary significantly by species and placental type. A biological model is presented in this article in which multinucleated trophoblast cells undergo apoptosis, releasing cffDNA that enters the maternal blood circulation after multinucleated trophoblast invasion. Advances in molecular biology technology have improved the ability to detect fetal-derived material, cells, DNA, and exosomes in maternal blood. However, notable research gaps remain for Mc in horses, goats, and pigs, highlighting the need for targeted studies to better understand species-specific patterns or a general biological model. Full article

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12 pages, 2070 KB

Open AccessArticle

Melatonin Receptor 1 and Melatonin Receptor 2 Expression During Human Kidney Development and Their Association with CAKUT

by Ann-Kathrin Schmitt, Victoria Tjora, Nela Kelam, Marija Jurić Gunjača, Petar Todorović, Clelia Picard, Manel Loche-Dalmon, Katarina Vukojević and Anita Racetin

J. Dev. Biol. 2026, 14(2), 18; https://doi.org/10.3390/jdb14020018 - 15 Apr 2026

Abstract

Background/Objectives: Growing evidence indicates that melatonin contributes to kidney development and function, while disruptions of fetal circadian signaling have been linked to congenital anomalies of the kidney and urinary tract (CAKUT). This study aimed to characterize the developmental and spatial expression patterns of [...] Read more.

Background/Objectives: Growing evidence indicates that melatonin contributes to kidney development and function, while disruptions of fetal circadian signaling have been linked to congenital anomalies of the kidney and urinary tract (CAKUT). This study aimed to characterize the developmental and spatial expression patterns of melatonin receptors MTNR1A and MTNR1B in normal human fetal kidneys and in CAKUT phenotypes. Methods: This study analyzed 40 human fetal kidney specimens, including healthy controls and CAKUT cases (horseshoe kidneys, duplex kidneys, and dysplastic kidneys), obtained from spontaneous abortions and pregnancy terminations. Samples were classified into developmental phases Ph2–Ph4 according to established morphological criteria. Immunofluorescence staining was used to visualize MTNR1A and MTNR1B expression. Quantitative analysis was performed using ImageJ, measuring the fluorescence area percentage. Statistical comparisons were conducted using a two-way ANOVA. Results: In control kidneys, MTNR1A expression was predominantly observed in glomeruli and interstitial cells and showed a descending trend across developmental stages, whereas MTNR1B was localized to glomeruli and strongly to the apical membranes of tubules, particularly distal tubules, without substantial developmental variation. CAKUT phenotypes exhibited higher expression of both receptors compared to controls. Significant phase-dependent differences in MTNR1A expression were observed in horseshoe, duplex, and dysplastic kidneys. MTNR1B expression decreased across developmental stages in dysplastic kidneys and differed significantly between Ph3 and Ph4 in duplex kidneys. At Ph3, duplex kidneys showed the highest MTNR1B expression. Conclusions: Altered developmental expression patterns of MTNR1A and MTNR1B in CAKUT suggest an association between melatonin signaling and abnormal human kidney development. Full article

(This article belongs to the Special Issue Developmental Biology of the Kidney: From Molecular Mechanisms to Congenital Disorders)

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13 pages, 1101 KB

Open AccessReview

Novel Functions and Potential of Ribosomes: From Cellular Transdifferentiation to Applications in Cell-Cultured Foods

by Shota Inoue, Hiroaki Hatano, Ikko Kawashima and Kunimasa Ohta

J. Dev. Biol. 2026, 14(2), 17; https://doi.org/10.3390/jdb14020017 - 9 Apr 2026

Abstract

Ribosomes are widely recognized as large intracellular macromolecular complexes responsible for protein synthesis. However, in recent years, numerous studies have revealed that ribosomal proteins possess non-canonical functions beyond translation, including roles in cell fate regulation, development, and disease. This review outlines emerging concepts [...] Read more.

Ribosomes are widely recognized as large intracellular macromolecular complexes responsible for protein synthesis. However, in recent years, numerous studies have revealed that ribosomal proteins possess non-canonical functions beyond translation, including roles in cell fate regulation, development, and disease. This review outlines emerging concepts surrounding the extracellular functions of ribosomes, with a particular focus on ribosome-induced cellular plasticity and transdifferentiation. Our studies have demonstrated that the incorporation of exogenous ribosomes reprograms somatic cells into a multipotent state and promotes differentiation into multiple lineages. These findings represent an alternative perspective to the conventional view of ribosomes as merely translational components. Furthermore, we discuss the biological significance of factors secreted by ribosome-incorporated cells by integrating the paracrine hypothesis with ribosome-mediated cell fate conversion. Finally, we explore the potential applications of ribosomes in regenerative medicine and cell-cultured food production. By redefining ribosomes as active regulators of cellular identity, this review provides a conceptual framework for understanding ribosome-driven cell fate regulation and its potential applications in sustainable biotechnology. Full article

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18 pages, 2706 KB

Open AccessArticle

Conserved Metanephric Kidney Development and Genome Methylation in Red-Eared Slider Turtle (Trachemys scripta elegans)

by Bing Jia, Mohamed Milad, Hannah C. Boehler, Adam Guerra, Joshua Mowry, Jessica Hiley, James Kasen Lisonbee, Michael Hafen and Troy Camarata

J. Dev. Biol. 2026, 14(2), 16; https://doi.org/10.3390/jdb14020016 - 7 Apr 2026

Abstract

Mammals and reptiles possess a metanephric kidney as the terminal renal organ for homeostasis of solutes and waste products. The development of the metanephric kidney has primarily been studied in mammalian model systems. Little is known about the conservation of metanephric kidney formation [...] Read more.

Mammals and reptiles possess a metanephric kidney as the terminal renal organ for homeostasis of solutes and waste products. The development of the metanephric kidney has primarily been studied in mammalian model systems. Little is known about the conservation of metanephric kidney formation in non-mammalian species such as reptiles. Uniquely, reptiles maintain kidney progenitor cell populations throughout life and continually develop new nephrons, the functional unit of the kidney. The red-eared slider turtle, Trachemys scripta elegans, was utilized to investigate the conservation of reptilian metanephric kidney development. The nephron progenitor cell (NPC) marker, Six2, was detected in whole-mount turtle kidneys in a similar pattern to mammals. However, there were differences in progenitor cell niche morphology where turtle NPC populations formed distinct elongated rows instead of the rosette-like morphology found in the mouse. The pattern of NPC populations in the embryonic turtle kidney was maintained in the adult turtle. Whole-genome bisulfite sequencing was performed on cortical tissue containing the NPC populations from adult turtle kidneys and compared to those of adult mice. Significant conservation of gene methylation was detected in adult cortical tissue between the two species, although unique signatures were detected in turtle samples related to DNA repair and β-catenin signaling. This suggests a high level of conservation of metanephric kidney development at the genetic level. Full article

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17 pages, 21451 KB

Open AccessArticle

Compensatory Serotonin Synthesis and Histone H3 Serotonylation in Preimplantation Embryos Exposed to Maternal Fluoxetine or Monoamine Oxidase Blockade

by Veronika S. Frolova and Denis A. Nikishin

J. Dev. Biol. 2026, 14(2), 15; https://doi.org/10.3390/jdb14020015 - 3 Apr 2026

Abstract

Serotonin is a critical morphogen in early development, yet the mechanisms regulating its homeostasis in the preimplantation embryo remain unclear, particularly under conditions of maternal antidepressant exposure. Here, we investigated embryonic serotonergic autonomy using mouse models of pharmacological transport blockade (maternal fluoxetine treatment) [...] Read more.

Serotonin is a critical morphogen in early development, yet the mechanisms regulating its homeostasis in the preimplantation embryo remain unclear, particularly under conditions of maternal antidepressant exposure. Here, we investigated embryonic serotonergic autonomy using mouse models of pharmacological transport blockade (maternal fluoxetine treatment) and in vitro treatment with the monoamine oxidase inhibitor pargyline. We employed immunofluorescence, RT-qPCR, and live-cell imaging to assess metabolic flux, gene expression, and physiological health. We demonstrate that monoamine oxidase functions as a metabolic firewall, progressively maturing from zygote to blastocyst to degrade excess amines. Paradoxically, maternal serotonin transporter blockade triggered significant intracellular serotonin hyper-accumulation in blastocysts, associated with a trend toward a compensatory upregulation of the biosynthetic gene Ddc. While this serotonin overload did not compromise morphology, mitochondrial function, or pluripotency marker expression, it induced a robust epigenetic response. Excess serotonin promoted elevated H3Q5ser immunoreactivity in both nuclear and cytoplasmic compartments via a transglutaminase-dependent mechanism. These findings reveal that the preimplantation embryo possesses a resilient, autonomous serotonergic system capable of compensatory synthesis. However, environmental fluctuations are chemically recorded via transglutaminase-mediated serotonylation, representing an epigenetic mark that warrants further long-term study within the Developmental Origins of Health and Disease (DOHaD) framework. Full article

(This article belongs to the Special Issue Genetic and Epigenetic Mechanisms in Gametogenesis and Early Development: Insights from Models, Stem Cells, and Human Disorders)

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19 pages, 494 KB

Open AccessReview

Transformation of the Biological Paradigm in Bone Regeneration: An Integrative Review

by Diyana Vladova

J. Dev. Biol. 2026, 14(1), 14; https://doi.org/10.3390/jdb14010014 - 11 Mar 2026

Abstract

Bone tissue is among the most commonly transplanted tissues worldwide. The treatment of critical-sized bone defects remains a significant challenge, as there is currently no universally accepted experimental model or therapeutic standard. Recent advances in fundamental cell biology are driving a paradigm shift [...] Read more.

Bone tissue is among the most commonly transplanted tissues worldwide. The treatment of critical-sized bone defects remains a significant challenge, as there is currently no universally accepted experimental model or therapeutic standard. Recent advances in fundamental cell biology are driving a paradigm shift in approaches to bone regeneration, highlighting the transformative potential of biofabrication technologies that integrate tissue engineering with personalized regenerative strategies. Three-dimensional (3D) bioprinting technology enables precise control over the architecture and spatial distribution of cellular and biologically active components, facilitating the creation of complex, personalized bone constructs. Central to this process are bioinks and biomaterials that mimic the extracellular matrix (ECM) and provide an optimal microenvironment for cellular function. Despite the substantial body of accumulated data, a comprehensive theoretical framework for functional bone biofabrication has not yet been fully established, emphasizing both the challenges and the innovative potential of the field. This integrative review synthesizes current knowledge on bone biology—from embryogenesis and cell–matrix interactions to molecular and neural regulation—and links it to the opportunities offered by biofabrication. Particular attention is given to bioinks as mediators between cell biology and engineering sciences, as well as to strategies for creating biomimetic ECM, optimizing scaffold design, and guiding future research toward clinically translatable bone regeneration. Full article

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18 pages, 1097 KB

Open AccessReview

SIX3 as a Regulator of Development and Disease

by Ana Beatriz Matos, Laura Jesus Castro and Torcato Martins

J. Dev. Biol. 2026, 14(1), 13; https://doi.org/10.3390/jdb14010013 - 6 Mar 2026

Abstract

Transcriptional regulation is pivotal for developmental processes and cell fate specification in homeostasis. One particularly relevant group of transcription factors is the sine oculis homeobox (SIX) family, which is involved in a wide range of molecular processes from development to tissue maintenance. Within [...] Read more.

Transcriptional regulation is pivotal for developmental processes and cell fate specification in homeostasis. One particularly relevant group of transcription factors is the sine oculis homeobox (SIX) family, which is involved in a wide range of molecular processes from development to tissue maintenance. Within this family, distinct subfamilies exhibit specific DNA-binding preferences and can function as transcriptional activators or repressors. In this review, we focus on the Optix/SIX3–SIX6 subfamily and discuss their roles as transcriptional regulators, as well as the consequences of their deregulation for neuronal and ocular development and for the maintenance of tissue homeostasis. We further examine how SIX3 can act either as a tumour suppressor or as a marker of poor prognosis in different cancer types. Moreover, we summarize recent findings on the role of SIX3 in pancreatic β cells and highlight emerging evidence that SIX2 also contributes to β-cell identity and regulatory stability. Downregulation of SIX2 and SIX3 alters gene regulatory programs associated with β-cell homeostasis and contributes to type 2 diabetes. As accumulating evidence links members of the SIX family to cancer and metabolic disease, it is crucial to characterize how these transcription factors regulate cell identity, with important implications for disease mechanisms and therapeutic strategies. Full article

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18 pages, 557 KB

Open AccessReview

Genomic Impacts of Biological Exposures

by Amalia S. Parra and Christopher A. Johnston

J. Dev. Biol. 2026, 14(1), 12; https://doi.org/10.3390/jdb14010012 - 5 Mar 2026

Abstract

Development and maintenance of complex tissues depends on a number of coordinated steps from early development through adulthood. These processes are fundamentally controlled by highly regulated gene expression patterns. Although critical contributors during development, intrinsic changes in gene expression alone cannot fully explain [...] Read more.

Development and maintenance of complex tissues depends on a number of coordinated steps from early development through adulthood. These processes are fundamentally controlled by highly regulated gene expression patterns. Although critical contributors during development, intrinsic changes in gene expression alone cannot fully explain the complicated pathways that control tissue homeostasis. Rather, tissues are continuously exposed to extrinsic factors that also influence essential cellular processes. These external environmental factors are collectively known as the exposome. Notably, how different exposures impact gene expression and protein function, as well as how certain exposures lead to disease states, is not well understood. To understand how internal and external factors influence organismal development and homeostasis, it is necessary to consider how genetic and nongenetic components interact to direct critical biochemical pathways. Doing so presents new avenues for precision medicine, understanding disease progression, identifying biological threats, and improving biological security concerns. In this review, we present recent advances in exposure biology, focusing on how these innovations can help identify novel biomarkers to better understand changing exposome components. We also discuss the need to integrate technologies and exposure research to better identify and predict threats. Full article

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16 pages, 2571 KB

Open AccessReview

Origins of Avian Hyperactive Mitochondria, Genome Compaction, and Air-Sac Physiology in Early Theropods During the Carnian Pluvial Episode

by Takumi Satoh

J. Dev. Biol. 2026, 14(1), 11; https://doi.org/10.3390/jdb14010011 - 2 Mar 2026

Abstract

Extant birds and the earliest dinosaurs may share fundamental metabolic features essential for aerobic exercise, suggesting that the extraordinary physical performance typical of avian species originated when dinosaurs first appeared during the Carnian Pluvial Episode (CPE). This physiological adaptation is complemented by hyperactive [...] Read more.

Extant birds and the earliest dinosaurs may share fundamental metabolic features essential for aerobic exercise, suggesting that the extraordinary physical performance typical of avian species originated when dinosaurs first appeared during the Carnian Pluvial Episode (CPE). This physiological adaptation is complemented by hyperactive mitochondria that exhibit high oxygen consumption and low reactive oxygen species production. Molecular genomics of fossils, the so-called “Jurassic Genome,” indicates that these early dinosaurs possessed compact genomes, 50–60% the size of the human genome, and small cells, implying a highly stringent metabolic regime. We suggest that hyperactive mitochondria, closely associated with compact genomes and small cells, drive theropod adaptation to the hot, dry, and hypoxic environments of the Late Triassic period, ultimately enabling their ecological dominance. Early dinosaurs such as Herrerasaurus are hypothesized to have possessed advanced physiological traits shared with modern birds, including hyperactive mitochondria, compact genomes, small cells, and a developing air-sac system. Collectively, these features most likely may have contributed to exceptional metabolic capacity, locomotor performance, and adaptation to the harsh environment of the CPE. Full article

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23 pages, 1633 KB

Open AccessSystematic Review

Evolutionary Restructuring and Systematic Review of the NBPF Gene Family: Comparative Genomics, Functional Divergence, and Disease-Linked Pathways

by Manuel Escalona and Rosa Roy

J. Dev. Biol. 2026, 14(1), 10; https://doi.org/10.3390/jdb14010010 - 24 Feb 2026

Abstract

The Neuroblastoma Breakpoint Family (NBPF) consists of 23 genes, 9 of which are pseudogenes, and is characterized by extensive duplication events and species-specific diversification in Homo sapiens, as well as by the presence of a unique protein domain known as Olduvai (also [...] Read more.

The Neuroblastoma Breakpoint Family (NBPF) consists of 23 genes, 9 of which are pseudogenes, and is characterized by extensive duplication events and species-specific diversification in Homo sapiens, as well as by the presence of a unique protein domain known as Olduvai (also referred to as DUF1220 or the NBPF domain). Previous studies have attempted to define subfamilies based on the presence of HLS triplet domains; however, this classification has become increasingly unclear with the identification of additional NBPF members. The family remains poorly understood, and the functions of many genes are still unknown, although several have been hypothesized to play key roles in cell proliferation and developmental processes, particularly in neural and skeletal tissues. In this study, we systematically analyzed all available data on the NBPF gene family using the PRISMA-S methodology to infer the biological functions in which these genes may be involved. We also generated multiple phylogenetic trees to support the creation of coherent subfamilies and to correlate the origin of each subfamily with homologous genes in our last common ancestor with the Pan genus, providing what we believe to be one of the most comprehensive phylogenetic reconstructions including all currently annotated NBPF members. Through comparative genomic and phylogenetic analyses, we propose that the NBPF may have originated from a duplication of the PDE4DIP gene, with NBPF26 representing the ancestral member from which the remaining NBPF genes diverged via lineage-specific segmental duplications. In this systematic review and comparative genomic study, we present the first integrative synthesis of our knowledge of the NBPF, encompassing its evolutionary origins, structural dynamics, expression across tissues, and clinical associations. Full article

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Journal of Developmental Biology

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