Drosophila Atg16 promotes enteroendocrine cell differentiation via regulation of intestinal Slit/Robo signaling.
Development
; 144(21): 3990-4001, 2017 11 01.
Article
en En
| MEDLINE
| ID: mdl-28982685
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 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.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Receptores Inmunológicos
/
Transducción de Señal
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Diferenciación Celular
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Células Enteroendocrinas
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Proteínas de Drosophila
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Drosophila melanogaster
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Proteínas Relacionadas con la Autofagia
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Mucosa Intestinal
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Proteínas del Tejido Nervioso
Límite:
Animals
Idioma:
En
Revista:
Development
Asunto de la revista:
BIOLOGIA
/
EMBRIOLOGIA
Año:
2017
Tipo del documento:
Article