PUBLICATION
Nuclear receptor Nr5a2 promotes diverse connective tissue fates in the jaw
- Authors
- Chen, H.J., Barske, L., Talbot, J.C., Dinwoodie, O.M., Roberts, R.R., Farmer, D.T., Jimenez, C., Merrill, A.E., Tucker, A.S., Crump, J.G.
- ID
- ZDB-PUB-230312-55
- Date
- 2023
- Source
- Developmental Cell 58(6): 461-473.e7 (Journal)
- Registered Authors
- Barske, Lindsey, Crump, Gage DeKoeyer, Talbot, Jared
- Keywords
- Nr5a2, craniofacial development, jaw, middle ear, multipotency, neural crest, salivary gland, tendon, zebrafish
- Datasets
- GEO:GSE210251
- MeSH Terms
-
- Animals
- Cell Differentiation/physiology
- Connective Tissue/metabolism
- Gene Expression Regulation, Developmental
- Mice
- Neural Crest/metabolism
- Receptors, Cytoplasmic and Nuclear*/metabolism
- Zebrafish*/metabolism
- Zebrafish Proteins/genetics
- Zebrafish Proteins/metabolism
- PubMed
- 36905926 Full text @ Dev. Cell
Citation
Chen, H.J., Barske, L., Talbot, J.C., Dinwoodie, O.M., Roberts, R.R., Farmer, D.T., Jimenez, C., Merrill, A.E., Tucker, A.S., Crump, J.G. (2023) Nuclear receptor Nr5a2 promotes diverse connective tissue fates in the jaw. Developmental Cell. 58(6):461-473.e7.
Abstract
Organ development involves the sustained production of diverse cell types with spatiotemporal precision. In the vertebrate jaw, neural-crest-derived progenitors produce not only skeletal tissues but also later-forming tendons and salivary glands. Here we identify the pluripotency factor Nr5a2 as essential for cell-fate decisions in the jaw. In zebrafish and mice, we observe transient expression of Nr5a2 in a subset of mandibular postmigratory neural-crest-derived cells. In zebrafish nr5a2 mutants, nr5a2-expressing cells that would normally form tendons generate excess jaw cartilage. In mice, neural-crest-specific Nr5a2 loss results in analogous skeletal and tendon defects in the jaw and middle ear, as well as salivary gland loss. Single-cell profiling shows that Nr5a2, distinct from its roles in pluripotency, promotes jaw-specific chromatin accessibility and gene expression that is essential for tendon and gland fates. Thus, repurposing of Nr5a2 promotes connective tissue fates to generate the full repertoire of derivatives required for jaw and middle ear function.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping