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Developmental Dynamics : An Official... Sep 2023Betaglycan, also known as the TGFβ type III receptor (Tgfbr3), is a co-receptor that modulates TGFβ family signaling. Tgfbr3 is upregulated during C2C12 myoblast...
BACKGROUND
Betaglycan, also known as the TGFβ type III receptor (Tgfbr3), is a co-receptor that modulates TGFβ family signaling. Tgfbr3 is upregulated during C2C12 myoblast differentiation and expressed in mouse embryos myocytes.
RESULTS
To investigate tgfbr3 transcriptional regulation during zebrafish embryonic myogenesis, we cloned a 3.2 kb promoter fragment that drives reporter transcription during C2C12 myoblasts differentiation and in the Tg(tgfbr3:mCherry) transgenic zebrafish. We detect tgfbr3 protein and mCherry expression in the adaxial cells concomitantly with the onset of their radial migration to become slow-twitch muscle fibers in the Tg(tgfbr3:mCherry). Remarkably, this expression displays a measurable antero-posterior somitic gradient expression.
CONCLUSIONS
tgfbr3 is transcriptionally regulated during somitic muscle development in zebrafish with an antero-posterior gradient expression that preferentially marks the adaxial cells and their descendants.
Topics: Animals; Mice; Zebrafish; Somites; Proteoglycans; Muscle Fibers, Slow-Twitch; Transforming Growth Factor beta; Muscle Development
PubMed: 37222488
DOI: 10.1002/dvdy.602 -
BioRxiv : the Preprint Server For... Jul 2023Shh signaling is the morphogen signaling that regulates embryonic craniofacial and neural tube development. G protein-coupled receptor 161 (Gpr161) is a negative...
Shh signaling is the morphogen signaling that regulates embryonic craniofacial and neural tube development. G protein-coupled receptor 161 (Gpr161) is a negative regulator of Shh signaling, and its inactivation in mice results in embryo lethality with craniofacial and neural tube defects (NTDs). However, the structural defects of later embryonic stages in null mice and cell lineages underlying abnormalities were not well characterized due to their limited lifespan. We found the lineage-specific deletion of in mice presented with tectal hypertrophy (anterior dorsal neuroepithelium), cranial vault and facial bone hypoplasia (cranial neural crest (CNC)), vertebral abnormalities (somite), and the closed form of spina bifida (posterior dorsal neuroepithelium). In particular, the closed form of spina bifida is partly due to the reduced and gene expression of the posterior dorsal neural tubes of mutant embryos involving decreased Wnt signaling whereas Shh signaling was increased. This study provides the novel role of Gpr161 in the posterior neural tube development and confirms its role on CNC- and somite-derived skeletogenesis and midbrain morphogenesis in mice.
PubMed: 37461574
DOI: 10.1101/2023.07.07.548129 -
Differentiation; Research in Biological... 2023The neural crest is a stem cell population that forms in the neurectoderm of all vertebrates and gives rise to a diverse set of cells such as sensory neurons, Schwann...
The neural crest is a stem cell population that forms in the neurectoderm of all vertebrates and gives rise to a diverse set of cells such as sensory neurons, Schwann cells and melanocytes. Neural crest development in snakes is still poorly understood. From the point of view of evolutionary and comparative anatomy is an interesting topic given the unique anatomy of snakes. The aim of the study was to characterize how trunk neural crest cells (TNCC) migrate in the developing elapid snake Naja haje haje and consequently, look at the beginnings of development of neural crest derived sensory ganglia (DRG) and spinal nerves. We found that trunk neural crest and DRG development in Naja haje haje is like what has been described in other vertebrates and the colubrid snake strengthening our knowledge on the conserved mechanisms of neural crest development across species. Here we use the marker HNK1 to follow the migratory behavior of TNCC in the elapid snake Naja haje haje through stages 1-6 (1-9 days postoviposition). We observed that the TNCC of both snake species migrate through the rostral portion of the somite, a pattern also conserved in birds and mammals. The development of cobra peripheral nervous system, using neuronal and glial markers, showed the presence of spectrin in Schwann cell precursors and of axonal plexus along the length of the cobra embryos. In conclusion, cobra embryos show strong conserved patterns in TNCC and PNS development among vertebrates.
Topics: Animals; Naja haje; Neural Crest; Peripheral Nervous System; Neurons; Organogenesis; Cell Movement; Mammals
PubMed: 37473561
DOI: 10.1016/j.diff.2023.06.002 -
Methods in Molecular Biology (Clifton,... 2024Paraxial mesoderm in the early embryo is segmented into epithelial blocks called somites that establish the metameric organization of the vertebrate body plan. Somites...
Paraxial mesoderm in the early embryo is segmented into epithelial blocks called somites that establish the metameric organization of the vertebrate body plan. Somites are sequentially formed from head to tail in a rhythmic manner controlled by an oscillating gene regulatory network known as the segmentation clock. We know very little about this important process during human development due to limited access to human embryos and ethical concerns. To bypass these difficulties, model systems derived from human pluripotent stem cells have been established. Here, we detail three protocols modeling different aspects of human paraxial mesoderm development in vitro: a 2D cell monolayer system recapitulating dynamics of the human segmentation clock, a 3D organoid system called "somitoid" supporting the simultaneous formation of somite-like structures, and another organoid system called "segmentoid" reconstituting in vivo-like hallmarks of somitogenesis. Together, these complementary model systems provide an excellent platform to decode somitogenesis and advance human developmental biology.
Topics: Animals; Humans; Mesoderm; Somites; Vertebrates; Pluripotent Stem Cells; Embryonic Development; Gene Expression Regulation, Developmental; Body Patterning
PubMed: 37843773
DOI: 10.1007/7651_2023_507 -
Toxicology and Applied Pharmacology Jun 2024Aripiprazole (ARI) is a recently developed antipsychotic medication that belongs to the second generation of antipsychotics. The literature has contradictory information...
INTRODUCTION
Aripiprazole (ARI) is a recently developed antipsychotic medication that belongs to the second generation of antipsychotics. The literature has contradictory information regarding ARI, which has been classified as pregnant use category C by the FDA.
METHODS
125 pathogen-free fertilized eggs were incubated for 28 h and divided into five groups of 25 eggs each (including the control group), and 18 eggs with intact integrity were selected from each group. After the experimental groups were divided, ARI was administered subblastodermally with a Hamilton micro-injector at 4 different doses (1 mg/kg, 5 mg/kg, 10 mg/kg, 20 mg/kg). At the 48th hour of incubation, all eggs were hatched and embryos were removed from the embryonic membranes. And then morphologic (position of the neural tube (open or closed), crown-rump length, number of somites, embryological development status), histopathologic (apoptosis (caspase 3), cell proliferation (PCNA), in situ recognition of DNA breaks (tunnel)), genetic (BRE gene expression) analyzes were performed.
RESULTS
According to the results of the morphological analysis, when the frequency of neural tube patency was evaluated among the experimental groups, a statistically significant difference was determined between the control group and all groups (p < 0.001). In addition, the mean crown-rump length and somite number of the embryos decreased in a dose-dependent manner compared to the control group. It was determined that mRNA levels of the BRE gene decreased in embryos exposed to ARI compared to the control group (p < 0.001).
CONCLUSION
Morphologically, histopathologically, and genetically, aripiprazole exposure delayed neurogenesis and development in early chick embryos. These findings suggest its use in pregnant women may be teratogenic. We note that these results are preliminary for pregnant women, but they should be expanded and studied with additional and other samples.
PubMed: 38906509
DOI: 10.1016/j.taap.2024.117009 -
Medecine Sciences : M/S Dec 2023The somites are embryonic structures that give rise to the axial musculoskeletal system. In amniotes vertebrates, somites are composed of multipotent somitic cells that...
The somites are embryonic structures that give rise to the axial musculoskeletal system. In amniotes vertebrates, somites are composed of multipotent somitic cells that quickly compartmentalize into a dorsal dermomyotome and a ventral sclerotome. In the somites, the dermomyotome gives rise to skeletal muscle cells (the myotome) and the dorsal dermis (the dermatome), while the sclerotome gives rise to vertebrae, ribs, and dorsal tendons (the syndetome). The compartmentalization pattern differs in anamniotes, with the establishment of a primitive myotome that begins before somite formation while the LSF (lateral somitic frontier) give rise to both the sclerotome and the dermomyotome in Xenopus. In this synthesis, we describe the contribution of the LSF in establishing somitic lineages in Xenopus and propose a model that traces the evolutionary history of somites back to ancestral precursors associated with striated skeletal muscle.
Topics: Humans; Animals; Somites; Xenopus laevis; Mesoderm; Muscle, Skeletal; Biological Evolution
PubMed: 38108728
DOI: 10.1051/medsci/2023181 -
Frontiers in Cell and Developmental... 2023Maternal diabetes during pregnancy is well known to be associated with a higher risk for structural birth defects in the offspring. Recent searches for underlying...
Maternal diabetes during pregnancy is well known to be associated with a higher risk for structural birth defects in the offspring. Recent searches for underlying mechanisms have largely focused on aberrant processes in the embryo itself, although prior research in rodent models implicated dysfunction also of the visceral yolk sac. The objective of our research was to investigate both tissues within the conceptus simultaneously. We conducted unbiased transcriptome profiling by RNA sequencing on pairs of individual yolk sacs and their cognate embryos, using the non-obese diabetic (NOD) mouse model. The analysis was performed at gestational day 8.5 on morphologically normal specimen to circumvent confounding by defective development. Even with large sample numbers ( = 33 in each group), we observed considerable variability of gene expression, primarily driven by exposure to maternal diabetes, and secondarily by developmental stage of the embryo. Only a moderate number of genes changed expression in the yolk sac, while in the embryo, the exposure distinctly influenced the relationship of gene expression levels to developmental progression, revealing a possible role for altered cell cycle regulation in the response. Also affected in embryos under diabetic conditions were genes involved in cholesterol biosynthesis and NAD metabolism pathways. Exposure to maternal diabetes during gastrulation changes transcriptomic profiles in embryos to a substantially greater effect than in the corresponding yolk sacs, indicating that despite yolk sac being of embryonic origin, different mechanisms control transcriptional activity in these tissues. The effects of maternal diabetes on expression of many genes that are correlated with developmental progression (i.e. somite stage) highlight the importance of considering developmental maturity in the interpretation of transcriptomic data. Our analyses identified cholesterol biosynthesis and NAD metabolism as novel pathways not previously implicated in diabetic pregnancies. Both NAD and cholesterol availability affect a wide variety of cellular signaling processes, and can be modulated by diet, implying that prevention of adverse outcomes from diabetic pregnancies may require broad interventions, particularly in the early stages of pregnancy.
PubMed: 37928898
DOI: 10.3389/fcell.2023.1273641 -
Journal of Oral Biosciences Mar 2024The tongue comprises multiple tissues of different embryonic origins, including pharyngeal arch, somite, and cranial neural crest (CNC). However, its developmental...
OBJECTIVES
The tongue comprises multiple tissues of different embryonic origins, including pharyngeal arch, somite, and cranial neural crest (CNC). However, its developmental regulatory mechanisms, especially those involving epigenetic modifiers, remain poorly understood. This study examined the roles of the epigenetic modifier G9a in murine tongue development.
METHODS
We deleted G9a using Sox 9 (SRY-related HMG-box gene 9)-Cre recombinase, which acts in tongue progenitor cells, including CNC-derived cells, to generate G9a conditional knockout (cKO) mice. Histochemical and immunohistochemical analyses were conducted on sections prepared from tongue tissues of control and cKO mice.
RESULTS
Cre-dependent LacZ reporter mice, generated by crossing Rosa-LacZ mice with sox9-Cre mice, revealed Cre recombinase activity in the mucosal epithelium and tongue connective tissue of the embryonic tongue. Tongue volume was significantly reduced on embryonic day 17.5 (E17.5) and postnatal day 0 (P0) in cKO mice. Histological sections showed that the lingual mucosal epithelium was thinner in cKO mice. Reduced G9a levels were accompanied by decreased levels of a G9a substrate, dimethylated lysine 9 in histone H3, in the embryonic tongue. BrdU injection at E16.5 revealed reduced numbers of BrdU-positive cells in the mucosal epithelium and underlying connective tissue at E17.5 in cKO mice, indicating suppression of cell proliferation in both tissues. Investigation of keratin 5 and 8 protein localization showed significantly suppressed expression in the lingual mucosal epithelium in cKO mice.
CONCLUSIONS
G9a is required for proper proliferation and differentiation of sox9-expressing tongue progenitor cells and is thereby involved in tongue development.
Topics: Animals; Mice; Bromodeoxyuridine; Cell Differentiation; Epigenesis, Genetic; Epithelium; Tongue
PubMed: 38142940
DOI: 10.1016/j.job.2023.12.007 -
Developmental Cell Apr 2024In bony fishes, patterning of the vertebral column, or spine, is guided by a metameric blueprint established in the notochord sheath. Notochord segmentation begins days...
In bony fishes, patterning of the vertebral column, or spine, is guided by a metameric blueprint established in the notochord sheath. Notochord segmentation begins days after somitogenesis concludes and can occur in its absence. However, somite patterning defects lead to imprecise notochord segmentation, suggesting that these processes are linked. Here, we identify that interactions between the notochord and the axial musculature ensure precise spatiotemporal segmentation of the zebrafish spine. We demonstrate that myoseptum-notochord linkages drive notochord segment initiation by locally deforming the notochord extracellular matrix and recruiting focal adhesion machinery at these contact points. Irregular somite patterning alters this mechanical signaling, causing non-sequential and dysmorphic notochord segmentation, leading to altered spine development. Using a model that captures myoseptum-notochord interactions, we find that a fixed spatial interval is critical for driving sequential segment initiation. Thus, mechanical coupling of axial tissues facilitates spatiotemporal spine patterning.
PubMed: 38697108
DOI: 10.1016/j.devcel.2024.04.013 -
IScience Dec 2023The cranial muscle is a critical component in the vertebrate head for a predatory lifestyle. However, its evolutionary origin and possible segmental nature during...
The cranial muscle is a critical component in the vertebrate head for a predatory lifestyle. However, its evolutionary origin and possible segmental nature during embryogenesis have been controversial. In jawed vertebrates, the presence of pre-otic segments similar to trunk somites has been claimed based on developmental observations. However, evaluating such arguments has been hampered by the paucity of research on jawless vertebrates. Here, we discovered different cellular arrangements in the head mesoderm in lamprey embryos () using serial block-face scanning electron and laser scanning microscopies. These cell populations were morphologically and molecularly different from somites. Furthermore, genetic comparison among deuterostomes revealed that mesodermal gene expression domains were segregated antero-posteriorly in vertebrates, whereas such segregation was not recognized in invertebrate deuterostome embryos. These findings indicate that the vertebrate head mesoderm evolved from the anteroposterior repatterning of an ancient mesoderm and developmentally diversified before the split of jawless and jawed vertebrates.
PubMed: 38187188
DOI: 10.1016/j.isci.2023.108338