Similar Datasets
Project description:Developmental potential is progressively restricted after germ layer specification during gastrulation. However, cranial neural crest cells challenge this paradigm, as they develop from anterior ectoderm, yet give rise to both ectodermal derivatives of the peripheral nervous system and ectomesenchymal bone and cartilage. How cranial neural crest cells differentiate into multiple lineages is poorly understood. Here, we demonstrate that cranial neural crest cells possess a transient state of increased chromatin accessibility. We profile the spatiotemporal emergence of premigratory neural crest and find evidence of lineage bias toward either a neuronal or ectomesenchymal fate, with each expressing distinct factors from earlier stages of development. We identify the miR-302 miRNA family to be highly expressed in cranial neural crest cells and genetic deletion leads to precocious specification of the ectomesenchymal lineage. Loss of mir-302 results in reduced chromatin accessibility in the neuronal progenitor lineage of neural crest and a reduction in peripheral neuron differentiation. Mechanistically, we find that mir-302 directly targets Sox9 to slow the timing of ectomesenchymal neural crest specification and represses multiple genes involved in chromatin condensation to promote accessibility required for neuronal differentiation. Our findings reveal a posttranscriptional mechanism governed by miRNAs to expand developmental potential of cranial neural crest.
| S-EPMC9963983 | biostudies-literature
Project description:Developmental potential is progressively restricted after germ layer specification during gastrulation. However, cranial neural crest cells challenge this paradigm, as they develop from anterior ectoderm yet give rise to both mesodermal derivatives of the craniofacial skeleton and ectodermal derivatives of the peripheral nervous system. How cranial neural crest cells differentiate into multiple lineages is poorly understood. Here, we demonstrate that cranial neural crest cells possess a transient state of increased chromatin accessibility; and that the earliest premigratory neural crest are biased towards either a neuronal or ectomesenchymal fate, with each lineage expressing distinct factors from the pluripotent state. We profile the spatiotemporal emergence of each neural crest population and demonstrate that the ectomesenchymal lineage forms prior to the neuronal progenitors. Expression of the pluripotency microRNA family miR-302 is maintained in cranial neural crest cells and genetic deletion leads to precocious specification of the ectomesenchymal lineage. We find that miR-302 directly targets Sox9 to slow the timing of ectomesenchyme induction and regulates multiple genes involved in chromatin condensation to maintain accessibility for neuronal differentiation. Loss of mir-302 results in reduced chromatin accessibility in the neuronal progenitor lineage of neural crest and a reduction in peripheral neuron differentiation. Our findings reveal a post-transcriptional mechanism governed by miRNAs from pluripotency as an important mechanism to expand developmental potential of cranial neural crest.
2022-10-25 | GSE216136 | GEO
Project description:Developmental potential is progressively restricted after germ layer specification during gastrulation. However, cranial neural crest cells challenge this paradigm, as they develop from anterior ectoderm yet give rise to both mesodermal derivatives of the craniofacial skeleton and ectodermal derivatives of the peripheral nervous system. How cranial neural crest cells differentiate into multiple lineages is poorly understood. Here, we demonstrate that cranial neural crest cells possess a transient state of increased chromatin accessibility; and that the earliest premigratory neural crest are biased towards either a neuronal or ectomesenchymal fate, with each lineage expressing distinct factors from the pluripotent state. We profile the spatiotemporal emergence of each neural crest population and demonstrate that the ectomesenchymal lineage forms prior to the neuronal progenitors. Expression of the pluripotency microRNA family miR-302 is maintained in cranial neural crest cells and genetic deletion leads to precocious specification of the ectomesenchymal lineage. We find that miR-302 directly targets Sox9 to slow the timing of ectomesenchyme induction and regulates multiple genes involved in chromatin condensation to maintain accessibility for neuronal differentiation. Loss of mir-302 results in reduced chromatin accessibility in the neuronal progenitor lineage of neural crest and a reduction in peripheral neuron differentiation. Our findings reveal a post-transcriptional mechanism governed by miRNAs from pluripotency as an important mechanism to expand developmental potential of cranial neural crest.
2022-10-25 | GSE215977 | GEO
Project description:Post-transcriptional regulation in cranial neural crest cells expands developmental potential
| PRJNA892136 | ENA
Project description:Post-transcriptional regulation in cranial neural crest cells expands developmental potential [II]
| PRJNA892142 | ENA
Project description:Post-transcriptional regulation in cranial neural crest cells expands developmental potential [I]
| PRJNA891631 | ENA
Project description:The cranial neural crest (CNC) explant assay was originally designed to assess the basic requirements for CNC migration in vitro. This protocol describes the key parameters of CNC explants in Xenopus laevis, with a focus on how to extirpate CNC cells and assay their migration in vitro. The protocol can be adapted according to the needs of the experimenter, some examples of which are discussed here.
| S-EPMC5834405 | biostudies-literature
Project description:The transplantation of cranial neural crest (CNC) expressing green fluorescent protein (GFP) in Xenopus laevis has allowed researchers not only to assess CNC migration in vivo but also to address many other experimental questions. Coupled with loss- or gain-of-function experiments, this technique can be used to characterize the function of specific genes during CNC migration and differentiation. Although targeted injection can also be used to assess gene function during CNC migration, CNC transplantation allows one to answer specific questions, such as whether a gene's function is tissue autonomous, cell autonomous, or exerted in the tissues surrounding the CNC. Here we describe a protocol for performing simple CNC grafts.
| S-EPMC6016762 | biostudies-literature
Project description:Ectodermal patterning is required for the establishment of multiple components of the vertebrate body plan. Previous studies have demonstrated that precise combinations of extracellular signals induce distinct ectodermal cell populations, such as the neural crest and the neural plate. Yet, we still lack understanding of how the response to inductive signals is modulated to generate the proper transcriptional output in target cells. Here we show that posttranscriptional attenuation of fibroblast growth factor (FGF) signaling is essential for the establishment of the neural crest territory. We found that neural crest progenitors display elevated expression of DICER, which promotes enhanced maturation of a set of cell-type-specific miRNAs. These miRNAs collectively target components of the FGF signaling pathway, a central player in the process of neural induction in amniotes. Inactivation of this posttranscriptional circuit results in a fate switch, in which neural crest cells are converted into progenitors of the central nervous system. Thus, the posttranscriptional attenuation of signaling systems is a prerequisite for proper segregation of ectodermal cell types. These findings demonstrate how posttranscriptional repression may alter the activity of signaling systems to generate distinct spatial domains of progenitor cells.
| S-EPMC7777031 | biostudies-literature
Project description:Microglossia is a congenital birth defect in humans and adversely impacts quality of life. In vertebrates, tongue muscle derives from the cranial mesoderm, whereas tendons and connective tissues in the craniofacial region originate from cranial neural crest (CNC) cells. Loss of transforming growth factor β (TGFβ) type II receptor in CNC cells in mice (Tgfbr2(fl/fl);Wnt1-Cre) causes microglossia due to a failure of cell-cell communication between cranial mesoderm and CNC cells during tongue development. However, it is still unclear how TGFβ signaling in CNC cells regulates the fate of mesoderm-derived myoblasts during tongue development. Here we show that activation of the cytoplasmic and nuclear tyrosine kinase 1 (ABL1) cascade in Tgfbr2(fl/fl);Wnt1-Cre mice results in a failure of CNC-derived cell differentiation followed by a disruption of TGFβ-mediated induction of growth factors and reduction of myogenic cell proliferation and differentiation activities. Among the affected growth factors, the addition of fibroblast growth factor 4 (FGF4) and neutralizing antibody for follistatin (FST; an antagonist of bone morphogenetic protein (BMP)) could most efficiently restore cell proliferation, differentiation, and organization of muscle cells in the tongue of Tgfbr2(fl/fl);Wnt1-Cre mice. Thus, our data indicate that CNC-derived fibroblasts regulate the fate of mesoderm-derived myoblasts through TGFβ-mediated regulation of FGF and BMP signaling during tongue development.
| S-EPMC3795273 | biostudies-literature