Pancreatic Cell Fate Determination Relies on Notch Ligand Trafficking by NFIA | Zendy

Marissa A. Scavuzzo | Zendy; Jolanta Chmielowiec | Zendy; Diane Yang | Zendy; Katrina Wamble | Zendy; Lesley Chaboub | Zendy; Lita Duraine | Zendy; Burak Tepe | Zendy; Stacey M. Glasgow | Zendy; Benjamin R. Arenkiel | Zendy; Christel Brou | Zendy; Benjamin Deneen | Zendy; Malgorzata Borowiak | Zendy

AI Assistant Blog Pricing

Home ZAIA Blog

Open Access

Pancreatic Cell Fate Determination Relies on Notch Ligand Trafficking by NFIA

Author(s) -

Marissa A. Scavuzzo,

Jolanta Chmielowiec,

Diane Yang,

Katrina Wamble,

Lesley Chaboub,

Lita Duraine,

Burak Tepe,

Stacey M. Glasgow,

Benjamin R. Arenkiel,

Christel Brou,

Benjamin Deneen,

Malgorzata Borowiak

Publication year - 2018

Publication title -

cell reports

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 6.264

H-Index - 154

eISSN - 2639-1856

pISSN - 2211-1247

DOI - 10.1016/j.celrep.2018.11.078

Subject(s) - notch signaling pathway , biology , microbiology and biotechnology , transcription factor , cell fate determination , progenitor cell , enteroendocrine cell , endocrine system , ectopic expression , pancreas , sox9 , cancer research , gene knockdown , stem cell , endocrinology , signal transduction , genetics , cell culture , gene , hormone

Notch is activated globally in pancreatic progenitors; however, for progenitors to differentiate into endocrine cells, they must escape Notch activation to express Neurogenin-3. Here, we find that the transcription factor nuclear factor I/A (NFIA) promotes endocrine development by regulating Notch ligand Dll1 trafficking. Pancreatic deletion of NFIA leads to cell fate defects, with increased duct and decreased endocrine formation, while ectopic expression promotes endocrine formation in mice and human pancreatic progenitors. NFIA-deficient mice exhibit dysregulation of trafficking-related genes including increased expression of Mib1, which acts to target Dll1 for endocytosis. We find that NFIA binds to the Mib1 promoter, with loss of NFIA leading to an increase in Dll1 internalization and enhanced Notch activation with rescue of the cell fate defects after Mib1 knockdown. This study reveals NFIA as a pro-endocrine factor in the pancreas, acting to repress Mib1, inhibit Dll1 endocytosis and thus promote escape from Notch activation.

The content you want is available to Zendy users.

Already have an account? Click here to sign in.

Having issues? You can contact us here

Accelerating Research