@article{d18728c543e14fffb8d5e0c32dff253b,
title = "Nuclear Receptor Nr5a2 Promotes Diverse Connective Tissue Fates in the Jaw",
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.",
author = "Hung-Jhen Chen and Lindsey Barske and Talbot, {Jarod C.} and Olivia Dinwoodie and Ryan Roberts and D'Juan Farmer and Christian Jimenez and Merrill, {Amy E.} and Tucker, {Abigail S.} and Crump, {J. Gage}",
note = "Funding Information: We thank Jenna Galloway for Tg(scxa:mCherry)fb301; the Broad CIRM Center Flow Cytometry Facility for FACS; the CHLA Center for Personalized Medicine Molecular Genomics Core for NGS sequencing; Megan Matsutani and Olivia Ruffins for fish care; and Samantha Brugmann for sharing the protocol of colorimetric whole-mount in situ for mouse embryos. Funding was provided by NIDCR R21DE029656 J.G.C. and A.E.M. and R35DE027550 to J.G.C. and HHMI Hannah H. Gray Fellows Program to D'J.T.F. O.M.D. was funded by the Medical Research Council KCL DTP. H.-J.C. and J.G.C. conceived the experiments. H.-J.C. conducted zebrafish and mouse experiments and data analysis. L.B. J.C.T. and C.J. initiated the categorization of zebrafish phenotypes. H.-J.C. O.M.D. R.R.R. A.E.M. A.S.T. and D'J.T.F. categorized mouse phenotypes. H.-J.C. R.R.R. and D'J.T.F. performed the single-nuclei multiome. J.G.C. A.E.M. and A.S.T. obtained funding and oversaw the project. H.-J.C. and J.G.C. wrote the manuscript. A.E.M. and A.S.T. reviewed and critiqued the manuscript. The authors declare no competing interests. One or more of the authors of this paper self-identifies as an underrepresented ethnic minority in their field of research or within their geographical location. One or more of the authors of this paper received support from a program designed to increase minority representation in their field of research. Funding Information: We thank Jenna Galloway for Tg(scxa:mCherry) fb301 ; the Broad CIRM Center Flow Cytometry Facility for FACS; the CHLA Center for Personalized Medicine Molecular Genomics Core for NGS sequencing; Megan Matsutani and Olivia Ruffins for fish care; and Samantha Brugmann for sharing the protocol of colorimetric whole-mount in situ for mouse embryos. Funding was provided by NIDCR R21DE029656 J.G.C. and A.E.M. and R35DE027550 to J.G.C. and HHMI Hannah H. Gray Fellows Program to D{\textquoteright}J.T.F. O.M.D. was funded by the Medical Research Council KCL DTP. Publisher Copyright: {\textcopyright} 2023 Elsevier Inc.",
year = "2023",
month = mar,
day = "27",
doi = "10.1016/j.devcel.2023.02.011",
language = "English",
volume = "58",
pages = "461--473.e7",
journal = "Developmental Cell",
issn = "1534-5807",
publisher = "Cell Press",
number = "6",
}