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Current Topics in Developmental Biology 2024In avian and mammalian embryos the "organizer" property associated with neural induction of competent ectoderm into a neural plate and its subsequent patterning into... (Review)
Review
In avian and mammalian embryos the "organizer" property associated with neural induction of competent ectoderm into a neural plate and its subsequent patterning into rostro-caudal domains resides at the tip of the primitive streak before neurulation begins, and before a morphological Hensen's node is discernible. The same region and its later derivatives (like the notochord) also have the ability to "dorsalize" the adjacent mesoderm, for example by converting lateral plate mesoderm into paraxial (pre-somitic) mesoderm. Both neural induction and dorsalization of the mesoderm involve inhibition of BMP, and the former also requires other signals. This review surveys the key experiments done to elucidate the functions of the organizer and the mechanisms of neural induction in amniotes. We conclude that the mechanisms of neural induction in amniotes and anamniotes are likely to be largely the same; apparent differences are likely to be due to differences in experimental approaches dictated by embryo topology and other practical constraints. We also discuss the relationships between "neural induction" assessed by grafts of the organizer and normal neural plate development, as well as how neural induction relates to the generation of neuronal cells from embryonic and other stem cells in vitro.
Topics: Animals; Mesoderm; Somites; Embryonic Induction; Birds; Mammals
PubMed: 38556458
DOI: 10.1016/bs.ctdb.2024.02.004 -
Environmental Science & Technology Oct 2023Synthetic glucocorticoids have been widely detected in aquatic ecosystems and may pose a toxicological risk to fish. In the present study, we described multiple end...
Synthetic glucocorticoids have been widely detected in aquatic ecosystems and may pose a toxicological risk to fish. In the present study, we described multiple end point responses of zebrafish to a commonly prescribed glucocorticoid, prednisolone (PREL), at concentrations between 0.001 and 9.26 μg/L. Of 23 end points monitored, 7 were affected significantly. Significant increases in the frequency of yolk extension formation, spontaneous contraction, heart rate, and ocular melanin density and significant decreases of ear-eye distance at PREL concentrations of 0.001 μg/L and above clearly pointed to the acceleration of embryonic development of zebrafish by PREL. Further confirmation came from the alterations in somite numbers, head-trunk angle, and yolk sac size, as well as outcomes obtained via RNA sequencing, in which signaling pathways involved in tissue/organ growth and development were highly enriched in embryos upon PREL exposure. In addition, the crucial role of glucocorticoid receptor (GR) for PREL-induced effects was confirmed by both, the coexposure to antagonist mifepristone (RU486) and GR mutant zebrafish experiments. We further demonstrated similar accelerations of embryonic development of zebrafish upon exposure to 11 additional glucocorticoids, indicating generic adverse effect characteristics. Overall, our results revealed developmental alterations of PREL in fish embryos at low concentrations and thus provided novel insights into the understanding of the potential environmental risks of glucocorticoids.
Topics: Animals; Glucocorticoids; Prednisolone; Zebrafish; Receptors, Glucocorticoid; Ecosystem; Embryonic Development; Embryo, Nonmammalian
PubMed: 37812749
DOI: 10.1021/acs.est.3c02658 -
International Journal of Molecular... Sep 2023represents a type of single-transmembrane adaptor protein containing an N-terminal cysteine-rich domain and a proline-rich C-terminal region. Nine subfamily genes have...
represents a type of single-transmembrane adaptor protein containing an N-terminal cysteine-rich domain and a proline-rich C-terminal region. Nine subfamily genes have been proposed in most vertebrates; however, some might be species-specific. The number of genes present in zebrafish remains unclear. This study aimed to investigate the evolutionary relationships among family genes in zebrafish (TU strain) using phylogenetic and syntenic analyses. The function of was preliminarily examined via CRISPR/Cas13d-mediated knockdown. Following identification in zebrafish, 10 family genes, namely , , , , , , , , , and , were classified into three main clades and six subclades. Their encoding proteins contained a cysteine-rich N-terminal domain and a proline-rich C-terminal region containing different motifs. A specific syntenic block containing and was observed to be conserved across all species. Furthermore, all these genes were expressed during embryogenesis. was expressed in the presomitic mesoderm, somites, and so on. was identified as a regulator of the expression of the somite formation marker . Overall, our study provides new insights into the evolution of family genes and the control of over the convergent extension cells of somitic precursors in zebrafish.
Topics: Animals; Zebrafish; Zebrafish Proteins; Phylogeny; Cysteine; Membrane Proteins; Proline; Gene Expression Regulation, Developmental
PubMed: 37762365
DOI: 10.3390/ijms241814062 -
Cells Sep 2023Purines are required for fundamental biological processes and alterations in their metabolism lead to severe genetic diseases associated with developmental defects whose...
Purines are required for fundamental biological processes and alterations in their metabolism lead to severe genetic diseases associated with developmental defects whose etiology remains unclear. Here, we studied the developmental requirements for purine metabolism using the amphibian as a vertebrate model. We provide the first functional characterization of purine pathway genes and show that these genes are mainly expressed in nervous and muscular embryonic tissues. Morphants were generated to decipher the functions of these genes, with a focus on the adenylosuccinate lyase (), which is an enzyme required for both salvage and de novo purine pathways. knockdown led to a severe reduction in the expression of the myogenic regulatory factors (MRFs: Myod1, Myf5 and Myogenin), thus resulting in defects in somite formation and, at later stages, the development and/or migration of both craniofacial and hypaxial muscle progenitors. The reduced expressions of and , which are two genes specific to the salvage and de novo pathways, respectively, resulted in similar alterations. In conclusion, our data show for the first time that de novo and recycling purine pathways are essential for myogenesis and highlight new mechanisms in the regulation of MRF gene expression.
Topics: Animals; Xenopus laevis; Muscle, Skeletal; Purines; Muscle Development
PubMed: 37830593
DOI: 10.3390/cells12192379 -
Disease Models & Mechanisms Nov 2023Sonic hedgehog (Shh) signaling is the morphogen signaling that regulates embryonic craniofacial and neural tube development. G protein-coupled receptor 161 (Gpr161) is...
Sonic hedgehog (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 associated with craniofacial defects and neural tube defects. However, the structural defects of later embryonic stages and cell lineages underlying abnormalities have not been well characterized due to the limited lifespan of Gpr161 null mice. We found that embryos with Pax3 lineage-specific deletion of Gpr161 presented with tectal hypertrophy (anterior dorsal neuroepithelium), cranial vault and facial bone hypoplasia (cranial neural crest), vertebral abnormalities (somite) and the closed form of spina bifida (posterior dorsal neuroepithelium). In particular, the closed form of spina bifida was partly due to reduced Pax3 and Cdx4 gene expression in the posterior dorsal neural tubes of Gpr161 mutant embryos with decreased Wnt signaling, whereas Shh signaling was increased. We describe a previously unreported role for Gpr161 in the development of posterior neural tubes and confirm its role in cranial neural crest- and somite-derived skeletogenesis and midbrain morphogenesis in mice.
Topics: Mice; Animals; Neural Tube; Hedgehog Proteins; Transcription Factors; Spinal Dysraphism; Embryonic Development; Wnt Signaling Pathway; Neurogenesis; Spine
PubMed: 37885410
DOI: 10.1242/dmm.050277 -
Clinical and Translational Science Jan 2024The generation of tissue from stem cells is an alluring concept as it holds a number of potential applications in clinical therapeutics and regenerative medicine.... (Review)
Review
The generation of tissue from stem cells is an alluring concept as it holds a number of potential applications in clinical therapeutics and regenerative medicine. Mesenchymal stromal/stem cells (MSCs) can be isolated from a number of different somatic sources, and have the capacity to differentiate into adipogenic, osteogenic, chondrogenic, and myogenic lineages. Although the first three have been extensively investigated, there remains a paucity of literature on the latter. This review looks at the various strategies available in vitro to enhance harvested MSC commitment and differentiation into the myogenic pathway. These include chemical inducers, myogenic-enhancing cell culture substrates, and mechanical and dynamic culturing conditions. Drawing on information from embryonic and postnatal myogenesis from somites, satellite, and myogenic progenitor cells, the mechanisms behind the chemical and mechanical induction strategies can be studied, and the sequential gene and signaling cascades can be used to monitor the progression of myogenic differentiation in the laboratory. Increased understanding of the stimuli and signaling mechanisms in the initial stages of MSC myogenic commitment will provide tools with which we can enhance their differentiation efficacy and advance the process to clinical translation.
Topics: Humans; Cells, Cultured; Cell Differentiation; Mesenchymal Stem Cells; Cell Culture Techniques; Muscle Development
PubMed: 38098144
DOI: 10.1111/cts.13703 -
BioRxiv : the Preprint Server For... Nov 2023Emerging human pluripotent stem cell (hPSC)-based embryo models are useful for studying human embryogenesis. Particularly, there are hPSC-based somitogenesis models...
Emerging human pluripotent stem cell (hPSC)-based embryo models are useful for studying human embryogenesis. Particularly, there are hPSC-based somitogenesis models using free-floating culture that recapitulate somite formation. Somitogenesis involves intricately orchestrated bio-chemical and -mechanical events. However, none of the current somitogenesis models controls biochemical gradients or biomechanical signals in the culture, limiting their applicability to untangle complex biochemical-biomechanical interactions that drive somitogenesis. Here we report a new human somitogenesis model by confining hPSC-derived presomitic mesoderm (PSM) tissues in microfabricated trenches. Exogenous microfluidic morphogen gradients imposed on PSM cause axial patterning and trigger spontaneous rostral-to-caudal somite formation. A mechanical theory is developed to explain the size dependency between somites and PSM. The microfluidic somitogenesis model is further exploited to reveal regulatory roles of cellular and tissue biomechanics in somite formation. This study presents a useful microengineered, hPSC-based model for understanding the bio-chemical and -mechanical events that guide somite formation.
PubMed: 37961125
DOI: 10.1101/2023.10.29.564399 -
Journal of Morphology Jan 2024In embryonic development, the vertebral column arises from the sclerotomal compartment of the somites. The sclerotome is a mesenchymal cell mass which can be subdivided... (Review)
Review
In embryonic development, the vertebral column arises from the sclerotomal compartment of the somites. The sclerotome is a mesenchymal cell mass which can be subdivided into several subpopulations specified by different regulatory mechanisms and giving rise to different parts of the vertebrae like vertebral body, vertebral arch, ribs, and vertebral joints. This review gives a short overview on the molecular and cellular basis of the formation of sclerotomal subdomains and the morphogenesis of their vertebral derivatives.
Topics: Animals; Cell Differentiation; Spine; Somites; Morphogenesis; Ribs
PubMed: 38100740
DOI: 10.1002/jmor.21665 -
Ecotoxicology and Environmental Safety Oct 2023Tris(2-chloroisopropyl) phosphate (TCIPP) is an organophosphate flame retardant detected in the environment and eggs, feathers, and livers. Early-developmental-stage...
Tris(2-chloroisopropyl) phosphate (TCIPP) is an organophosphate flame retardant detected in the environment and eggs, feathers, and livers. Early-developmental-stage avian embryos are vulnerable to the toxic effects of chemicals. However, studies on the specific effects of TCIPP on avian embryonic development are limited. We aimed to investigate the toxicity of TCIPP in early chicken embryos using a previously developed shell-less incubation system. Fertilized chicken (Gallus gallus domesticus) eggs (n = 220) were exposed to 50 or 500 nmol TCIPP/(g egg) or dimethyl sulfoxide (DMSO) as a vehicle control on Day 0 of incubation. Development of 198 embryos was monitored from Days 3-9 of incubation, and 22 embryos on Day 4 and 74 embryos on Day 9 were dissected. Messenger RNA expression levels for several genes were measured in embryos on Day 4. Both TCIPP-exposed groups showed a significant reduction in survival rate. Imaging analyses revealed significant decreases in body length, head and bill length, eye diameter, and forelimb and hindlimb length in both TCIPP-treated groups. TCIPP exposure significantly impaired the development of extraembryonic blood vessels and the production of red blood cells. A TCIPP-dose-dependent decreasing trend in heart rate was observed on Days 4-7. The somitic angle increased significantly on Days 4-6, and embryos with curved somites showed cleavage in the back and gaps between somites, resulting in asymmetrical somite formation. A significant correlation was found between the somitic angle and FGF8 expression levels, suggesting that TCIPP exposure affects somite formation through an altered FGF-signaling pathway. Embryos with somitic deformities in TCIPP-exposed groups had significantly reduced survival rates, indicating that abnormal segment formation directly increased mortality. Finally, eye weight and ocular luminosity values were significantly reduced, suggesting that TCIPP may also affect eye development. Overall, these findings highlight severe toxic effects of TCIPP on avian embryonic development, including in vascularization, cardiac function, and somite and ocular development.
Topics: Animals; Chick Embryo; Chickens; Phosphates; Flame Retardants; Organophosphorus Compounds; Organophosphates
PubMed: 37690177
DOI: 10.1016/j.ecoenv.2023.115445 -
International Journal of Molecular... Sep 2023Sialidases remove terminal sialic acids residues from the non-reducing ends of glycoconjugates. They have been recognized as catabolic enzymes that work within different...
Sialidases remove terminal sialic acids residues from the non-reducing ends of glycoconjugates. They have been recognized as catabolic enzymes that work within different subcellular compartments and can ensure the proper turn-over of glycoconjugates. Four mammalian sialidases (NEU1-4) exist, with different subcellular localization, pH optimum and substrate specificity. In zebrafish, seven different sialidases, with high homology to mammalian counterparts, have been identified. Zebrafish Neu3.2 is similar to the human cytosolic sialidase NEU2, which is involved in skeletal muscle differentiation and exhibits a broad substrate specificity toward gangliosides and glycoproteins. In zebrafish , mRNA is expressed during somite development, and its enzymatic activity has been detected in the skeletal muscle and heart of adult animals. In this paper, 1-4-cell-stage embryos injected with splice-blocking morpholino showed severe embryonic defects, mainly in somites, heart and anterior-posterior axis formation. and expressions were altered in morphants, and impaired musculature formation was associated with a defective locomotor behavior. Finally, the co-injection of mouse mRNA in morphants rescued the phenotype. These data are consistent with the involvement of cytosolic sialidase in pathologies related to muscle formation and support the validity of the model to investigate the pathogenesis of the diseases.
Topics: Animals; Down-Regulation; Muscle Development; Muscle, Skeletal; Neuraminidase; Zebrafish; Zebrafish Proteins
PubMed: 37686385
DOI: 10.3390/ijms241713578