Control of cranial ectomesenchyme fate by Nr2f nuclear receptors
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ABSTRACT:
PROVIDER: PRJNA852585 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR19846950_1.fastq.gz | Fastqsanger.gz | |||
| SRR19846950_2.fastq.gz | Fastqsanger.gz | |||
| SRR19846951_1.fastq.gz | Fastqsanger.gz | |||
| SRR19846951_2.fastq.gz | Fastqsanger.gz | |||
| SRR19846952_1.fastq.gz | Fastqsanger.gz |
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Project description:Certain cranial neural crest cells are uniquely endowed with the ability to make skeletal cell types otherwise only derived from mesoderm. As these cells migrate into the pharyngeal arches, they downregulate neural crest specifier genes and upregulate so-called ectomesenchyme genes characteristic of skeletal progenitors. While both external and cell-autonomous factors have been proposed as triggers of this transition, the details remain obscure. Here we report the Nr2f nuclear receptors as novel intrinsic activators of the ectomesenchyme program: zebrafish nr2f5 and nr2f2; nr2f5 mutants show a marked delay in upregulation of ectomesenchyme genes such as dlx2a, prrx1a/b, sox9a, twist1a, and fli1a, and in downregulation of the non-ectomesenchyme specifier sox10. Depending on genotype, mutants partially or fully recover, likely via functional redundancy with other Nr2f genes. Loss of sox10 fully rescued skeletal development in nr2f5 single but not nr2f2; nr2f5 double mutants, while the ectomesenchyme defect persisted in both. Sox10 perdurance thus antagonizes the recovery rather than causing the initial aberration. Unraveling the mechanics of Nr2f function will help solve the enduring puzzle of how cranial neural crest acquire skeletal potency.
2022-11-07 | GSE206903 | GEO
Project description:Nuclear receptors are iteratively deployed during neural crest development, from pre-induction through differentiation stages. NR2F1 and NR2F2 in particular have been proposed as broad regulators of early neural crest gene expression in mammals, but the timing, extent, and redundancy of their developmental requirement has remained unclear, as Nr2f1 and Nr2f2 single mouse mutants present only minimal craniofacial phenotypes. Here we report the dynamic expression patterns of Nr2f1 and Nr2f2 in the mouse cranial neural crest from specification through post-migratory stages. Combined conditional knockout of both Nr2f1 and Nr2f2 in the neural crest with Wnt1-Cre or Pax3Cre caused severe midfacial clefting, loss of the maxilla and palate, and hypoplasticity of all other facial skeletal elements except the distal mandible. These perinatal phenotypes were rooted in a major shortage of pharyngeal arch mesenchyme at mid-gestation. This in turn traced to a deficiency of migrating neural crest cells, first evident in the trailing part of the first arch migratory stream at embryonic day 8.75. RNAseq at a slightly earlier stage revealed downregulation of many migratory neural crest genes, including a possible direct target, the phospholipase Plcg2. These findings reveal a vital requirement for NR2F1/2 within the later-forming cranial neural crest.
2025-10-15 | GSE295092 | GEO
Project description:Cranial neural crest shortage leads to extensive craniofacial anomalies in mice mutant for the NR2F1/2 nuclear receptors
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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.
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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.
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Project description:Neural crest cells are embryonic progenitors that generate numerous cell types in vertebrates. With single cell analysis, we show that mouse trunk neural crest cells become biased toward neuronal lineages when they delaminate from the neural tube, whereas cranial neural crest cells acquire ectomesenchyme potential dependent on activation of the transcription factor Twist1. The choices that neural crest cells make to become sensory, glial, autonomic, or mesenchymal cells can be formalized as a series of sequential binary decisions. Each branch of the decision tree involves initial co-activation of bipotential properties followed by gradual shifts towards commitment. Competing fate programs are co-activated before cells acquire fate-specific phenotypic traits. Determination of a specific fate is achieved by increased synchronization of relevant programs and concurrent repression of competing fate programs.
2019-04-02 | GSE129114 | GEO
Project description:Purpose: The cranial suture is a fibrous joint, and similar to the growth plates of the skeletal long bone, they serve as the major centers of calvarial vault morphogenesis. Our group’s identification of a skeletal stem cell isolated from the mouse tibial growth plate prompted us to investigate whether these skeletal stem cells are also resident in the mouse cranial sutures and if they govern postnatal suture patency or fusion. Results: We preformed a spatio-temporal profiling of the mouse cranial sutures by flow cytometry, demonstrating a significant decrease in the temporal representation of skeletal stem cells in fusing versus patent sutures. Moreover, canonical Wnt signaling has a significant impact on skeletal stem cells proliferation and thus representation within the suture, dictating fate: fusion or patency. Breeding an Axin2+/-LacZ mouse, with enhanced activation of canonical Wnt signaling to a Twist1+/− mouse, harboring a coronal craniosynostosis enriched the skeletal stem cell pool in coronal sutures, thereby preventing Twist1+/− craniosynostosis. Conclusions: Our findings suggest an imbalance and/or decrease in resident skeletal stem cells within the cranial sutures gives rise to craniosynostosis, however, restoring this representation by enriching skeletal stem cells within the suture can maintain patency.
2020-04-15 | GSE138880 | GEO
Project description:Purpose: The cranial suture is a fibrous joint, and similar to the growth plates of the skeletal long bone, they serve as the major centers of calvarial vault morphogenesis. Our group’s identification of a skeletal stem cell isolated from the mouse tibial growth plate prompted us to investigate whether these skeletal stem cells are also resident in the mouse cranial sutures and if they govern postnatal suture patency or fusion. Results: We preformed a spatio-temporal profiling of the mouse cranial sutures by flow cytometry, demonstrating a significant decrease in the temporal representation of skeletal stem cells in fusing versus patent sutures. Moreover, canonical Wnt signaling has a significant impact on skeletal stem cells proliferation and thus representation within the suture, dictating fate: fusion or patency. Breeding an Axin2+/-LacZ mouse, with enhanced activation of canonical Wnt signaling to a Twist1+/− mouse, harboring a coronal craniosynostosis enriched the skeletal stem cell pool in coronal sutures, thereby preventing Twist1+/− craniosynostosis. Conclusions: Our findings suggest an imbalance and/or decrease in resident skeletal stem cells within the cranial sutures gives rise to craniosynostosis, however, restoring this representation by enriching skeletal stem cells within the suture can maintain patency.
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Project description:Skeletal Stem Cell Powering Cranial Suture Fate: An Answer to Craniosynostosis
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2014-10-29 | E-GEOD-60764 | biostudies-arrayexpress