title: Enteric neural crest-derived cells promote their migration by modifying their microenvironment through tenascin-C production.
abstract: The enteric nervous system (ENS) is derived from vagal and sacral neural crest cells that migrate, proliferate, and differentiate into enteric neurons and glia within the gut wall. The mechanisms regulating enteric neural crest-derived cell (ENCC) migration are poorly characterized despite the importance of this process in gut formation and function. Characterization of genes involved in ENCC migration is essential to understand ENS development and could provide targets for treatment of human ENS disorders. We identified the extracellular matrix glycoprotein tenascin-C (TNC) as an important regulator of ENCC development. We find TNC dynamically expressed during avian gut development. It is absent from the cecal region just prior to ENCC arrival, but becomes strongly expressed around ENCCs as they enter the ceca and hindgut. In aganglionic hindguts, TNC expression is strong throughout the outer mesenchyme, but is absent from the submucosal region, supporting the presence of both ENCC-dependent and independent expression within the gut wall. Using rat-chick coelomic grafts, neural tube cultures, and gut explants, we show that ENCCs produce TNC and that this ECM protein promotes their migration. Interestingly, only vagal neural crest-derived ENCCs express TNC, whereas sacral neural crest-derived cells do not. These results demonstrate that vagal crest-derived ENCCs actively modify their microenvironment through TNC expression and thereby help to regulate their own migration.
authors: Department of Pediatric Surgery, Massachusetts General Hospital, Harvard Medical School, Warren 1153, Boston, MA 02114, USA.
authors: Sophia E
authors: SE
authors: Akbareian
authors: Nandor
authors: N
authors: Nagy
authors: Casey E
authors: CE
authors: Steiger
authors: John D
authors: JD
authors: Mably
authors: Sarah A
authors: SA
authors: Miller
authors: Ryo
authors: R
authors: Hotta
authors: David
authors: D
authors: Molnar
authors: Allan M
authors: AM
authors: Goldstein
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D002465:Cell Movement / Q000235:genetics*; D002642:Chick Embryo; D004622:Embryo, Mammalian; D017615:Enteric Nervous System / Q000166:cytology / Q000196:embryology; D009432:Neural Crest / Q000166:cytology / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D019063:Tenascin / Q000096:biosynthesis*
chemical_list: D019063:Tenascin
keywords: Enteric nervous system; Extracellular matrix; Hirschsprung disease; Neural crest cells; Tenascin-C
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