Drosophila Atg16 promotes enteroendocrine cell differentiation via regulation of intestinal Slit/Robo signaling.
Péter NagyZsuzsanna SzatmáriGyöngyvér O SándorMónika LippaiKrisztina HegedűsGábor JuhászPublished in: Development (Cambridge, England) (2017)
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 the WD40 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 domain-specific Atg16 mutants indicates that their stem cell niche regulatory function is independent of autophagy. Our study reveals how mutations in these different genes may contribute to IBD.
Keyphrases
- stem cells
- induced apoptosis
- inflammatory response
- cell cycle arrest
- endoplasmic reticulum stress
- signaling pathway
- cell death
- cell therapy
- oxidative stress
- ulcerative colitis
- single cell
- transcription factor
- immune response
- gene expression
- dna methylation
- hiv infected
- antiretroviral therapy
- men who have sex with men