Drosophila atg16 promotes enteroendocrine cell differentiation via regulation of intestinal Slit/Robo signaling

Péter Nagy, Zsuzsanna Szatmári, Gyöngyvér O. Sándor, Mónika Lippai, Krisztina Hegedűs, Gábor Juhász

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Genetic variations of Atg16l1, Slit2 and Rab19 predispose to the development of inflammatory bowel disease (IBD), but the relationship between these mutations is unclear. Here we show that in Drosophila guts lacking theWD40 domain of Atg16, pre-enteroendocrine (pre-EE) cells accumulate that fail to differentiate into properly functioning secretory EE cells. Mechanistically, loss of Atg16 or its binding partner Rab19 impairs Slit production, which normally inhibits EE cell generation by activating Robo signaling in stem cells. Importantly, loss of Atg16 or decreased Slit/Robo signaling triggers an intestinal inflammatory response. Surprisingly, analysis of Rab19 and domainspecific Atg16 mutants indicates that their stem cell niche regulatory function is independent of autophagy. Our study reveals howmutations in these different genes may contribute to IBD.

Original languageEnglish
Pages (from-to)3990-4001
Number of pages12
JournalDevelopment (Cambridge)
Volume144
Issue number21
DOIs
Publication statusPublished - Nov 1 2017

Keywords

  • Atg16
  • Drosophila
  • Inflammation
  • Intestine
  • Rab19
  • Slit

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology

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