{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T11:52:40Z","timestamp":1787313160011,"version":"build-2736575974"},"reference-count":46,"publisher":"American Society for Clinical Investigation","issue":"3","license":[{"start":{"date-parts":[[2026,2,2]],"date-time":"2026-02-02T00:00:00Z","timestamp":1769990400000},"content-version":"vor","delay-in-days":55,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"GRF","award":["HKU17107322,HKU17111824"],"award-info":[{"award-number":["HKU17107322,HKU17111824"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,2,2]]},"abstract":"<jats:p>\n                    Vinculin (VCL), a linker between cells and their environment, has rarely been linked to disease. This study examines the role of VCL in the development of the enteric nervous system (ENS) and its relationship to Hirschsprung disease (HSCR). Using whole-genome sequencing and in vitro assays, we identified 4\n                    <jats:italic>VCL<\/jats:italic>\n                    mutations associated with HSCR, most causing loss of function. Neural crest\u2013specific\n                    <jats:italic>Vcl<\/jats:italic>\n                    knock-out mice (\n                    <jats:italic>Vcl<\/jats:italic>\n                    cKO) displayed ENS defects resembling short-segment HSCR, including partial colonic aganglionosis and abnormal gut musculature. Single-cell transcriptomics revealed dysregulation of genes involved in neuronal differentiation and MAPK signaling. Spatial RNA-seq revealed reduced ENS-mesenchyme interactions in\n                    <jats:italic>Vcl<\/jats:italic>\n                    cKO mice, accompanied by significant disruption of the Pleiotrophin (PTN) pathway;\n                    <jats:italic>Ptn<\/jats:italic>\n                    knock-out mice exhibited phenotypes similar to those of\n                    <jats:italic>Vcl<\/jats:italic>\n                    cKO mice, underscoring the importance of ENS-mesenchyme crosstalk. VCL works as a hub gene crucial for cell connection and signaling pathways essential for ENS formation.\n                    <jats:italic>VCL<\/jats:italic>\n                    deficiency subtly impacts various developmental stages and neighboring cells, cumulatively leading to a phenotype similar to short-segment HSCR. This research highlights the role of VCL in maintaining cellular interactions and signaling pathways, such as MAPK and PTN, which are crucial for ENS development and may inform therapeutic targets for ENS disorders.\n                  <\/jats:p>","DOI":"10.1172\/jci198531","type":"journal-article","created":{"date-parts":[[2025,12,9]],"date-time":"2025-12-09T17:00:52Z","timestamp":1765299652000},"source":"Crossref","is-referenced-by-count":2,"title":["Vinculin influences essential processes in enteric nervous system development and Hirschsprung disease pathogenesis"],"prefix":"10.1172","volume":"136","author":[{"given":"Lifang","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Surgery and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xixin","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Surgery 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