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Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2023,8,22]]},"abstract":"<jats:p>\n                    The receptor tyrosine kinase RET plays a critical role in the fate specification of enteric neural crest\u2013derived cells (ENCDCs) during enteric nervous system (ENS) development.\n                    <jats:italic>RET<\/jats:italic>\n                    loss of function (LoF) is associated with Hirschsprung disease (HSCR), which is marked by aganglionosis of the gastrointestinal (GI) tract. Although the major phenotypic consequences and the underlying transcriptional changes from\n                    <jats:italic>Ret<\/jats:italic>\n                    LoF in the developing ENS have been described, cell type- and state-specific effects are unknown. We performed single-cell RNA sequencing on an enriched population of ENCDCs from the developing GI tract of\n                    <jats:italic>Ret<\/jats:italic>\n                    null heterozygous and homozygous mice at embryonic day (E)12.5 and E14.5. We demonstrate four significant findings: 1)\n                    <jats:italic>Ret<\/jats:italic>\n                    -expressing ENCDCs are a heterogeneous population comprising ENS progenitors as well as glial- and neuronal-committed cells; 2) neurons committed to a predominantly inhibitory motor neuron developmental trajectory are not produced under\n                    <jats:italic>Ret<\/jats:italic>\n                    LoF, leaving behind a mostly excitatory motor neuron developmental program; 3) expression patterns of HSCR-associated and\n                    <jats:italic>Ret<\/jats:italic>\n                    gene regulatory network genes are impacted by\n                    <jats:italic>Ret<\/jats:italic>\n                    LoF; and 4)\n                    <jats:italic>Ret<\/jats:italic>\n                    deficiency leads to precocious differentiation and reduction in the number of proliferating ENS precursors. Our results support a model in which\n                    <jats:italic>Ret<\/jats:italic>\n                    contributes to multiple distinct cellular phenotypes during development of the ENS, including the specification of inhibitory neuron subtypes, cell cycle dynamics of ENS progenitors, and the developmental timing of neuronal and glial commitment.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2211986120","type":"journal-article","created":{"date-parts":[[2023,8,16]],"date-time":"2023-08-16T13:44:30Z","timestamp":1692193470000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":38,"title":["<i>Ret<\/i>\n                    deficiency decreases neural crest progenitor proliferation and restricts fate potential during enteric nervous system development"],"prefix":"10.1073","volume":"120","author":[{"given":"Elizabeth","family":"Vincent","sequence":"first","affiliation":[{"name":"McKusick-Nathans Department of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sumantra","family":"Chatterjee","sequence":"additional","affiliation":[{"name":"Center for Human Genetics and Genomics, New York University Grossman School of Medicine, New York, NY 10016"},{"name":"Department of Neuroscience and Physiology, New York University Grossman School of Medicine, New York, NY 10016"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabrielle H.","family":"Cannon","sequence":"additional","affiliation":[{"name":"McKusick-Nathans Department of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dallas","family":"Auer","sequence":"additional","affiliation":[{"name":"McKusick-Nathans Department of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Holly","family":"Ross","sequence":"additional","affiliation":[{"name":"McKusick-Nathans Department of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aravinda","family":"Chakravarti","sequence":"additional","affiliation":[{"name":"Center for Human Genetics and Genomics, New York University Grossman School of Medicine, New York, NY 10016"},{"name":"Department of Neuroscience and Physiology, New York University Grossman School of Medicine, New York, NY 10016"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2875-451X","authenticated-orcid":false,"given":"Loyal A.","family":"Goff","sequence":"additional","affiliation":[{"name":"McKusick-Nathans Department of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205"},{"name":"Solomon H. 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