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<p>Enteric neural crest cells (ENCCs) colonize the gut during embryogenesis and migration defects give rise to Hirschsprung disease (HD). Mutations in GDNF/RET and EDN3/EDNRB are known to be causal in HD. Here, we show that migrating ENCCs in mice exhibit endogenous EDN3/EDNRB-gated calcium activity, mediated by chloride channels, T-type Ca<sup>2+</sup> channels and inositol trisphosphate-sensitive intracellular-store release. We find that inhibiting Ca<sup>2+</sup> activity results in ENCC migration defects, while exciting it promotes migration by increasing ENCC contractility and traction force to the extracellular matrix. Our study demonstrates that embryonic endothelin-mediated neural crest migration and adult endothelin-mediated vasoconstriction is one and the same phenomenon, taking place in different cell types. Our results suggest a functional link between rare mutations of <i>CACNA1H</i> (the gene encoding CaV3.2) and HD, and pave the way for understanding neurocristopathies in terms of neural crest cell bioelectric activity deficits.</p>

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Endothelin-3 and T-type Ca2+ channels drive enteric neural crest cell calcium activity, contractility and migration

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年1月20日

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  • Nicolas R. Chevalier,
  • Fanny Gayda,
  • Nadège Bondurand,
  • Ze Chi Chan,
  • Thierry Savy,
  • Monique Frain,
  • Amira El Merhie,
  • Lenuta Canta,
  • Monica Dicu,
  • Isabelle Le Parco,
  • Léna Zig

摘要

Enteric neural crest cells (ENCCs) colonize the gut during embryogenesis and migration defects give rise to Hirschsprung disease (HD). Mutations in GDNF/RET and EDN3/EDNRB are known to be causal in HD. Here, we show that migrating ENCCs in mice exhibit endogenous EDN3/EDNRB-gated calcium activity, mediated by chloride channels, T-type Ca2+ channels and inositol trisphosphate-sensitive intracellular-store release. We find that inhibiting Ca2+ activity results in ENCC migration defects, while exciting it promotes migration by increasing ENCC contractility and traction force to the extracellular matrix. Our study demonstrates that embryonic endothelin-mediated neural crest migration and adult endothelin-mediated vasoconstriction is one and the same phenomenon, taking place in different cell types. Our results suggest a functional link between rare mutations of CACNA1H (the gene encoding CaV3.2) and HD, and pave the way for understanding neurocristopathies in terms of neural crest cell bioelectric activity deficits.