Search Results (73)

The adrenal medulla and organs of Zuckerkandl consist of chromaffin cells that produce, store, and secrete catecholamines. In humans, the adrenal medulla is known to function throughout postnatal life, while the organs of Zuckerkandl degenerate by 2–3 years of postnatal life. Although the history of investigation of chromaffin cells goes back more than a century, little is known about the reciprocal organogenesis of the adrenal glands and organs of Zuckerkandl during human fetal development. In the current study, we compared these two organs using serial sectioning, routine histological staining, and immunohistochemical reactions in human embryos, prefetuses, and fetuses from 8 to 26 gestational weeks. In our study, we used antibodies for tyrosine hydroxylase, dopamine beta-hydroxylase, and phenylethanolamine N-methyltransferase, which are enzymes of catecholamine synthesis, β-III tubulin, and S100. We found two morphological cell types (large and small) in the developing ganglia, organs of Zuckerkandl, and adrenal medulla, and two migration patterns of large cells and small cells. The immunohistochemical characteristics of these cells were determined. We revealed that the number of small cells increased significantly at the ages from 16 to 21–22 gestational weeks, followed by a decrease at 22.5–26 gestational weeks. The presence of two large cell subpopulations was suggested—those that migrate primarily from organs of the Zuckerkandl region and those that differentiate later from the small cells. We also determined that 12 gestational weeks was the age of the first appearance of phenylethanolamine N-methyltransferase reactivity in developing chromaffin cells, temporally correlating with synaptogenesis events. This is important data in the light of the controversial glucocorticoid theory of phenylethanolamine N-methyltransferase induction in humans. Full article

Rabbit meat constitutes a high-protein, low-fat nutritional resource demonstrating rising consumption, particularly within the Asia-Pacific region. Consequently, muscle growth and developmental pattern in meat rabbits represent critical economic considerations. To elucidate the primary signaling pathways governing muscle development, we first performed comparative body weight analyses between two rabbit breeds exhibiting divergent growth rates: the fast-growing Checkered Giant (Ju) and slow-growing Sichuan Ma rabbit. Subsequent, post-natal qualities of thigh and longissimus dorsi muscle fiber were quantified across three developmental phases (28, 56, and 84 days post-natal). The results showed the body weight of Ju rabbit was significantly higher than that of Ma rabbit beyond 3 weeks post-natal (p < 0.05), while Ma rabbit exhibited larger muscle fiber areas in both tissues at 56 days (p < 0.05). The transcriptome analysis showed that 284 and 305 differentially expressed genes (DEGs) (|log2FC| > 1, padj < 0.05) were identified in thigh muscle and longissimus dorsi muscle, respectively. GO (Gene Ontology) analysis of DEGs indicated DEGs in the thigh muscle were enriched in these terms related to biological processes of muscle cell migration and smooth muscle cell migration, cellular components of sarcomere, myofibril, and actin filament bundle, while DEGs in longissimus dorsi muscle were enriched in these terms associated with biological processes of muscle cell migration, smooth muscle cell migration and muscle structure development, cellular component of actin cytoskeleton, contractile fiber, myofibril, myosin complex and molecular function of actin filament binding. Integrated GO, KEGG and PPI analyses of co-expressive DEGs implicated the HIF-1 signaling pathway and Glycolysis/Gluconeogenesis in muscular development. Different expression of energy metabolism hub-genes might be the primary reason for interbreed muscle developmental disparities. Full article

The young mammalian central nervous system regenerates after spinal cord injury and recovers locomotion, whereas adult mice only show limited recovery that depends on the injury severity, genetic background, and physical therapy. At the molecular level, key regulators that contribute to recovery are cell adhesion molecules, such as L1CAM (L1). At the cell surface, L1 functions as a homotypic receptor that signal-transduces crucial functions in neuronal migration and survival, neurite outgrowth, myelination, formation of synapses, and synaptic plasticity. In the adult central nervous system, L1 is expressed only by neurons. We now show that L1 is unexpectedly also expressed by 26% microglia, freshly isolated from a 7-day-old mouse brain. At postnatal day 21, only 3% of microglia are L1-positive. Using a mouse mutant in which L1 is deleted specifically in monocytes of 10- to 14-week-old mice, functional recovery was reduced up to 4 weeks after injury at lower thoracic spinal levels. Also, NF200-immunoreactive and 5-HT-immunoreactive fibers were found decreased below the injury site as compared to wild-type mice. In conclusion, microglial cells that express L1 stimulate neurite outgrowth in vitro, improve functional recovery after spinal cord injury in adult mice, and increase fiber densities caudal to the lesion site. Full article

Low birth weight (LBW) in various species leads to a pronounced skeletal muscle phenotype and can serve as a model to study muscle formation and draw conclusions for normal and pathological development. We aimed to elucidate in detail how the differentiation of muscular stem cells and their progeny are disturbed in piglets born with LBW. We isolated primary muscle cells from LBW piglets and their normal siblings with two different approaches: (1) single cells from two functionally divergent subpopulations (previously named “fast” and “slow”) and (2) cells derived from isolated, intact myofibers. Subsequently, we analyzed their proliferative and differentiative capacity by determining proliferation rate, migration behavior, myotube formation, and myogenic gene and protein expression. LBW led to a decreased proliferation rate and migration potential in cells from the subpopulation fast group. Cells from LBW piglets were generally able to differentiate, but they formed smaller myotubes with less incorporated nuclei, leading to a diminished fusion rate. Myogenic gene expression was also significantly altered due to pig birth weight. Overall, early postnatal muscle development in LBW was disturbed at several crucial steps involving the establishment of a reserve stem cell pool, movement of cells towards existing myofibers, and the ability to form nascent myofibers. Full article

Background: Prenatal alcohol exposure (PAE) models can cause neurodevelopmental abnormalities like those observed in fetal alcohol spectrum disorder (FASD). Previous studies link experimental PAE effects in the brain to impaired signaling through insulin/IGF and Notch pathways that mediate neuronal survival, growth, migration, energy metabolism, and plasticity. Importantly, concurrent administration of peroxisome proliferator-activated receptor agonists or dietary soy prevented many aspects of FASD due to their insulin-sensitizing, anti-inflammatory, and antioxidant properties. Objective: To determine if dietary soy interventions during pregnancy would be sufficient to normalize central nervous system structure and function, we examined the effects of maternal gestation-limited dietary soy on cerebellar postnatal development, motor function, and critical signaling pathways. Methods: Pregnant Long Evans rats were fed isocaloric liquid diets containing 0% or 26% caloric ethanol with casein or soy isolate as the protein source. The ethanol and soy feedings were discontinued upon delivery. The offspring were subjected to rotarod motor function tests, and on postnatal day 35, they were sacrificed to harvest cerebella for histological and molecular studies. Results: Despite the postnatal cessation of alcohol exposure, chronic gestational exposure reduced brain weight, caused cerebellar hypoplasia, and impaired motor performance. Gestational dietary soy prevented the ethanol-associated reduction in brain weight and largely restored the histological integrity of the cerebellum but failed to normalize motor performance. Ethanol withdrawal abolished the impairments in insulin/IGF signaling that were previously associated with ongoing ethanol exposures, but ethanol’s inhibitory effects on Notch and Wnt signaling persisted. Soy significantly increased cerebellar expression of the insulin and IGF-1 receptors and abrogated several ethanol-associated impairments in Notch and Wnt signaling. Conclusions: Although gestation-restricted dietary soy has significant positive effects on neurodevelopment, optimum prevention of FASD’s long-term effects will likely require dietary soy intervention during the critical periods of postnatal development, even after alcohol exposures have ceased. Full article

Macrophages play important roles in metabolic dysfunction-associated steatohepatitis (MASH), an advanced and inflammatory stage of metabolic dysfunction-associated steatotic liver disease (MASLD). In humans and mice, the cellular heterogeneity and diverse function of hepatic macrophages in MASH have been investigated by single cell RNA sequencing (scRNA-seq). However, little is known about their roles in rats. Here, we collected liver tissues at the postnatal week 16, when our previously characterized Lep^{∆I14/∆I14} rats developed MASH phenotypes. By scRNA-seq, we found an increase in the number of macrophages and endothelial cells and a decrease in that of NK and B cells. Hepatic macrophages in rats underwent a unique M1 to M2 transition without expression of the classical markers such as Arg1 and Nos2, except for Cd163. Lipid-associated macrophages (LAMs) were increased, which could be detected by the antibody against Cd63. In the microenvironment, macrophages had an increased number of interactions with hepatocytes, myofibroblasts, T cells, neutrophils, and dendritic cells, while their interaction strengths remained unchanged. Finally, the macrophage migration inhibitory factor (MIF) pathway was identified as the top upregulated cell-communication pathway in MASH. In conclusion, we dissected hepatic macrophage dynamics during MASH at single cell resolution and provided fundamental tools for the investigation of MASH in rat models. Full article

(1) Background: Crossed fused renal ectopia is a rare migration and fusion renal anomaly, more frequently affecting males, with an incidence of between 1:2000 and 1:7500 observed at autopsy. (2) Case presentation: This paper presents the case of a 34-year-old woman, IIIG IIIP, who presented to our clinic for a first-trimester screening evaluation. The risk calculation was performed using the Fetal Medicine Foundation’s first-trimester screening software, version 2.8.1. The screening indicated a low risk for aneuploidies, but the ultrasound scan revealed an empty right renal fossa in the standard coronal section. A more detailed axial examination raised the suspicion of crossed fused renal ectopia. No other anomalies were detected. The morphological scans conducted in the second and third trimesters confirmed and upheld the diagnosis initially established in the first trimester. The fetus did not develop any potential antepartum complications. The patient gave birth via caesarean section at 36 weeks to a live female infant, weighing 3000 g, with an APGAR score of 9 at 1 min. Postnatally, the first trimester diagnosis of the renal malformation was confirmed. (3) Conclusions: Crossed fused renal ectopia, probably the rarest renal migration anomaly, can be diagnosed as early as the first trimester of pregnancy. Full article

A complete understanding of neural crest cell mechanodynamics during ocular development will provide insight into postnatal neural crest cell contributions to ophthalmic abnormalities in adult tissues and inform regenerative strategies toward injury repair. Herein, single-cell RNA sequencing in zebrafish during early eye development revealed keratin intermediate filament genes krt8 and krt18a.1 as additional factors expressed during anterior segment development. In situ hybridization and immunofluorescence microscopy confirmed krt8 and krt18a.1 expression in the early neural plate border and migrating cranial neural crest cells. Morpholino oligonucleotide (MO)-mediated knockdown of K8 and K18a.1 markedly disrupted the migration of neural crest cell subpopulations and decreased neural crest cell marker gene expression in the craniofacial region and eye at 48 h postfertilization (hpf), resulting in severe phenotypic defects reminiscent of neurocristopathies. Interestingly, the expression of K18a.1, but not K8, is regulated by retinoic acid (RA) during early-stage development. Further, both keratin proteins were detected during postnatal corneal regeneration in adult zebrafish. Altogether, we demonstrated that both K8 and K18a.1 contribute to the early development and postnatal repair of neural crest cell-derived ocular tissues. Full article

Pregnancy is a particularly vulnerable period for the growing fetus, when exposure to toxic agents, especially in the early phases, can decisively harm embryo development and compromise the future health of the newborn. The inclusion of various chemical substances in personal care products (PCPs) and cosmetic formulations can be associated with disruption and damage to the nervous system. Microplastics, benzophenones, parabens, phthalates and metals are among the most common chemical substances found in cosmetics that have been shown to induce neurotoxic mechanisms. Although cosmetic neurotoxin exposure is believed to be minimal, different exposure scenarios of cosmetics suggest that these neurotoxins remain a threat. Special attention should be paid to early exposure in the first weeks of gestation, when critical processes, like the migration and proliferation of the neural crest derived cells, start to form the ENS. Importantly, cosmetic neurotoxins can cross the placental barrier and affect the future embryo, but they are also secreted in breast milk, so babies remain exposed for longer periods, even after birth. In this review, we explore how neurotoxins contained in cosmetics and PCPs may have a role in the pathogenesis of various neurodevelopmental disorders and neurodegenerative diseases and, therefore, also in congenital enteric aganglionosis as well as in postnatal motility disorders. Understanding the mechanisms of these chemicals used in cosmetic formulations and their role in neurotoxicity is crucial to determining the safety of use for cosmetic products during pregnancy. Full article

Phosphatase and tensin homolog (Pten) is a key regulator of cell proliferation and a potential target to stimulate postnatal enteric neuro- and/or gliogenesis. To investigate this, we generated two tamoxifen-inducible Cre recombinase murine models in which Pten was conditionally ablated, (1) in glia (Plp1-expressing cells) and (2) in neurons (Calb2-expressing cells). Tamoxifen-treated adult (7–12 weeks of age; n = 4–15) mice were given DSS to induce colitis, EdU to monitor cell proliferation, and were evaluated at two timepoints: (1) early (3–4 days post-DSS) and (2) late (3–4 weeks post-DSS). We investigated gut motility and evaluated the enteric nervous system. Pten inhibition in Plp1-expressing cells elicited gliogenesis at baseline and post-DSS (early and late) in the colon, and neurogenesis post-DSS late in the proximal colon. They also exhibited an increased frequency of colonic migrating motor complexes (CMMC) and slower whole gut transit times. Pten inhibition in Calb2-expressing cells did not induce enteric neuro- or gliogenesis, and no alterations were detected in CMMC or whole gut transit times when compared to the control at baseline or post-DSS (early and late). Our results merit further research into Pten modulation where increased glia and/or slower intestinal transit times are desired (e.g., short-bowel syndrome and rapid-transit disorders). Full article

Heart disease is a pressing public health problem and the leading cause of death worldwide. The heart is the first organ to gain function during embryogenesis in mammals. Heart development involves cell determination, expansion, migration, and crosstalk, which are orchestrated by numerous signaling pathways, such as the Wnt, TGF-β, IGF, and Retinoic acid signaling pathways. Human-induced pluripotent stem cell-based platforms are emerging as promising approaches for modeling heart disease in vitro. Understanding the signaling pathways that are essential for cardiac development has shed light on the molecular mechanisms of congenital heart defects and postnatal heart diseases, significantly advancing stem cell-based platforms to model heart diseases. This review summarizes signaling pathways that are crucial for heart development and discusses how these findings improve the strategies for modeling human heart disease in vitro. Full article

In Alzheimer’s disease, the blood–brain barrier breakdown, blood vessel damage and re-organization are early events. Deposits of the small toxic peptide beta-amyloid (Aβ) cause the formation of extracellular plaques and accumulate in vessels disrupting the blood flow but may also play a role in blood clotting. In the present study, we aim to explore the impact of Aβ on the migration of endothelial cells and subsequent vessel formation. We use organotypic brain slices of postnatal day 10 wildtype mice (C57BL/6) and connect them to small microcontact prints (µCPs) of collagen. Our data show that laminin-positive endothelial cells migrate onto collagen µCPs, but without any vessel formation after 4 weeks. When the µCPs are loaded with human Aβ40, (aggregated) human Aβ42 and mouse Aβ42 peptides, the number and migration distance of endothelial cells are significantly reduced, but with a more pronounced subsequent vessel formation. The vessel formation is verified by zonula occludens (ZO)-1 and -2 stainings and confocal microscopy. In addition, the vessel formation is accompanied by a stronger GFAP-positive astroglial formation. Finally, we show that vessels can grow towards convergence when two opposed slices are connected via microcontact-printed lanes. In conclusion, our data show that Aβ promotes vessel formation, and organotypic brain slices connected to collagen µCPs provide a potent tool to study vessel formation. Full article

The interplay of the enteric nervous system (ENS) and SIP syncytium (smooth muscle cells–interstitial cells of Cajal–PDGFRα+ cells) plays an important role in the regulation of gastrointestinal (GI) motility. This study aimed to investigate the dynamic regulatory mechanisms of the ENS-SIP system on colon motility during postnatal development. Colonic samples of postnatal 1-week-old (PW1), 3-week-old (PW3), and 5-week-old (PW5) mice were characterized by RNA sequencing, qPCR, Western blotting, isometric force recordings (IFR), and colonic motor complex (CMC) force measurements. Our study showed that the transcriptional expression of Pdgfrα, c-Kit, P2ry1, Nos1, and Slc18a3, and the protein expression of nNOS, c-Kit, and ANO1 significantly increased with age from PW1 to PW5. In PW1 and PW3 mice, colonic migrating movement was not fully developed. In PW5 mice, rhythmic CMCs were recorded, similar to the CMC pattern described previously in adult mice. The inhibition of nNOS revealed excitatory and non-propulsive responses which are normally suppressed due to ongoing nitrergic inhibition. During postnatal development, molecular data demonstrated the establishment and expansion of ICC and PDGFRα+ cells, along with nitrergic and cholinergic nerves and purinergic receptors. Our findings are important for understanding the role of the SIP syncytium in generating and establishing CMCs in postnatal, developing murine colons. Full article

The epicardium is a very dynamic cardiac layer with pivotal contributions during cardiogenesis, acting in the postnatal period as an apparently dormant single-cell layer. In mammalian embryos, the epicardium, which originates form the proepicardium, translocates into the pericardial cavity and subsequently rests on the surface of the myocardium. Later, it gives rise to the epicardium-derived cells, which migrate into subepicardial space, invade the developing myocardium, promoting its growth, and contribute to different cell types. Anomalies in the process of epicardial development, the generation of epicardium-derived cells and their signaling mechanisms in different experimental models lead to defective cardiac development, reminiscent of human congenital heart diseases. Furthermore, recent studies have reported that epicardial derivates in adults, i.e., epicardial adipose tissue, are associated with electrophysiological cardiovascular anomalies. Herein, we provide a state-of-the-art review focusing on both congenital and adult heart diseases associated with epicardial development. Full article

Black women in the UK face significantly higher risks of overweight and obesity and adverse pregnancy outcomes compared to women from other ethnic groups. Maternal nutrition plays a pivotal role in influencing the health outcomes of women and their children, especially during preconception and pregnancy. Cultural and environmental factors significantly influence the dietary experiences of African women after migration. This study explored the unique nutrition-related challenges faced by African migrant pregnant and postnatal women in the UK, and their nutrition support needs. Interviews were conducted with 23 African migrant women living in the UK, who were either pregnant or had a pregnancy within the past 3 years. These were analysed thematically, resulting in five overarching themes: food rituals and beliefs, pregnancy cravings, limited access to culturally appropriate food, limited access to culturally appropriate and evidence-based nutritional guidance, and the focus on healthy weight. The study identified challenges that African migrant women face in balancing their cultural heritage with the UK food environment and dietary recommendations, including potential implications on their health and pregnancy outcomes. It emphasised the importance of addressing these challenges through culturally sensitive approaches and tailored interventions, to enable informed decision making and enhance health outcomes for these women. Full article