{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,2,23]],"date-time":"2026-02-23T07:44:38Z","timestamp":1771832678092,"version":"3.50.1"},"posted":{"date-parts":[[2024,9,19]]},"group-title":"Developmental Biology","reference-count":76,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2024,9,19]],"date-time":"2024-09-19T00:00:00Z","timestamp":1726704000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.biorxiv.org\/about\/FAQ#license"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2024,9,19]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:sec>\n                  <jats:title>Background &amp; Aims<\/jats:title>\n                  <jats:p>\n                    Enteric nervous system (ENS) development requires migration, proliferation, and appropriate neuronal diversification from progenitors to enable normal gastrointestinal (GI) motility.\n                    <jats:italic>Sox10<\/jats:italic>\n                    deficit causes aganglionosis, modeling Hirschsprung disease, and disrupts ratios of postnatal enteric neurons in proximal ganglionated bowel. How\n                    <jats:italic>Sox10<\/jats:italic>\n                    deficiency alters ratios of enteric neuron subtypes is unclear.\n                    <jats:italic>Sox10\u2019s<\/jats:italic>\n                    prominent expression in enteric neural crest-derived progenitors (ENCP) and lack of this gene in enteric neurons led us to examine\n                    <jats:italic>\n                      Sox10\n                      <jats:sup>Dom<\/jats:sup>\n                    <\/jats:italic>\n                    effects ENS progenitors and early differentiating enteric neurons.\n                  <\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>\n                    ENS progenitors, developing neurons, and enteric glia were isolated from\n                    <jats:italic>\n                      Sox10\n                      <jats:sup>+\/+<\/jats:sup>\n                    <\/jats:italic>\n                    and\n                    <jats:italic>\n                      Sox10\n                      <jats:sup>Dom\/+<\/jats:sup>\n                    <\/jats:italic>\n                    littermates for single-cell RNA sequencing (scRNA-seq). scRNA-seq data was processed to identify cell type-specific markers, differentially expressed genes, cell fate trajectories, and gene regulatory network activity between genotypes. Hybridization chain reaction (HCR) validated expression changes detected in scRNA-seq.\n                  <\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>\n                    scRNA-seq profiles revealed three neuronal lineages emerging from cycling progenitors via two transition pathways accompanied by elevated activity of\n                    <jats:italic>Hox<\/jats:italic>\n                    gene regulatory networks (GRN) as progenitors transition to neuronal fates.\n                    <jats:italic>\n                      Sox10\n                      <jats:sup>Dom\/+<\/jats:sup>\n                    <\/jats:italic>\n                    scRNA-seq profiles exhibited a novel progenitor cluster, decreased abundance of cells in transitional states, and shifts in cell distributions between two neuronal trajectories.\n                    <jats:italic>Hoxa6<\/jats:italic>\n                    was differentially expressed in the neuronal lineages impacted in\n                    <jats:italic>\n                      Sox10\n                      <jats:sup>Dom\/+<\/jats:sup>\n                    <\/jats:italic>\n                    mutants and HCR identified altered\n                    <jats:italic>Hoxa6<\/jats:italic>\n                    expression in early developing neurons of\n                    <jats:italic>\n                      Sox10\n                      <jats:sup>Dom\/+<\/jats:sup>\n                    <\/jats:italic>\n                    ENS.\n                  <\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>\n                    <jats:italic>\n                      Sox10\n                      <jats:sup>Dom\/+<\/jats:sup>\n                    <\/jats:italic>\n                    mutation shifts enteric neuron types by altering neuronal trajectories during early ENS lineage segregation. Multiple neurogenic transcription factors are reduced in\n                    <jats:italic>\n                      Sox10\n                      <jats:sup>Dom\/+<\/jats:sup>\n                    <\/jats:italic>\n                    scRNA-seq profiles including multiple\n                    <jats:italic>Hox<\/jats:italic>\n                    genes. This is the first report that implicates\n                    <jats:italic>Hox<\/jats:italic>\n                    genes in lineage diversification of enteric neurons.\n                  <\/jats:p>\n                <\/jats:sec>","DOI":"10.1101\/2024.09.18.613729","type":"posted-content","created":{"date-parts":[[2024,9,19]],"date-time":"2024-09-19T07:50:21Z","timestamp":1726732221000},"source":"Crossref","is-referenced-by-count":1,"title":["Single Cell Profiling in the\n                  <i>\n                    Sox10\n                    <sup>Dom\/+<\/sup>\n                  <\/i>\n                  Hirschsprung Mouse Implicates\n                  <i>Hoxa6<\/i>\n                  in Enteric Neuron Lineage Allocation"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8780-7610","authenticated-orcid":false,"given":"Justin A.","family":"Avila","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7078-837X","authenticated-orcid":false,"given":"Joseph T.","family":"Benthal","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2505-5457","authenticated-orcid":false,"given":"Jenny C.","family":"Schafer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4718-5869","authenticated-orcid":false,"given":"E. 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