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| Status |
Public on Nov 07, 2022 |
| Title |
Control of cranial ectomesenchyme fate by Nr2f nuclear receptors |
| Organism |
Danio rerio |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
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.
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| Overall design |
Bulk RNA-seq was performed on FACS-purified zebrafish neural crest cells expressing sox10:DsRed from 20 hpf nr2f2[unknown]; nr2f5[mutant] embryos (2 replicates: n = 88 & 35) and wild-type control embryos (2 replicates: n = 110 & 120).
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| Contributor(s) |
Barske L, Okeke C, Paulding D, Riedel A, Paudel S, Phelan C, Teng C |
| Citation(s) |
36367707 |
| Submission date |
Jun 24, 2022 |
| Last update date |
Feb 14, 2023 |
| Contact name |
Lindsey Barske |
| E-mail(s) |
lindsey.barske@cchmc.org
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| Organization name |
Cincinnati Children's Hospital Medical Center
|
| Department |
Human Genetics
|
| Street address |
3333 Burnet Ave MLC 7016
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| City |
Cincinnati |
| State/province |
OH |
| ZIP/Postal code |
45229 |
| Country |
USA |
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| Platforms (1) |
| GPL14875 |
Illumina HiSeq 2000 (Danio rerio) |
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| Samples (4)
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| GSM6266709 |
sox10:DsRed+ neural crest cells from 20 hpf nr2f2;nr2f5 mutant embryos - biol rep 1 |
| GSM6266710 |
sox10:DsRed+ neural crest cells from 20 hpf nr2f2;nr2f5 mutant embryos - biol rep 2 |
| GSM6266711 |
sox10:DsRed+ neural crest cells from 20 hpf wild-type embryos - biol rep 1 |
| GSM6266712 |
sox10:DsRed+ neural crest cells from 20 hpf wild-type embryos - biol rep 2 |
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| Relations |
| BioProject |
PRJNA852585 |
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