The bHLH transcription factor Mist1 is required to maintain exocrine pancreas cell organization and acinar cell identity

Citation
Cl. Pin et al., The bHLH transcription factor Mist1 is required to maintain exocrine pancreas cell organization and acinar cell identity, J CELL BIOL, 155(4), 2001, pp. 519-530
Citations number
56
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Cell & Developmental Biology
Journal title
JOURNAL OF CELL BIOLOGY
ISSN journal
0021-9525 → ACNP
Volume
155
Issue
4
Year of publication
2001
Pages
519 - 530
Database
ISI
SICI code
0021-9525(20011112)155:4<519:TBTFMI>2.0.ZU;2-8
Abstract
The pancreas is a complex organ that consists of separate endocrine and exo crine cell compartments. Although great strides have been made in identifyi ng regulatory factors responsible for endocrine pancreas formation, the mol ecular regulatory circuits that control exocrine pancreas properties are ju st beginning to be elucidated. In an effort to identify genes involved in e xocrine pancreas function, we have examined Mist1, a basic helix-loop-helix transcription factor expressed in pancreatic acinar cells. Mist1-null (Mis t1(KO)) mice exhibit extensive disorganization of exocrine tissue and intra cellular enzyme activation. The exocrine disorganization is accompanied by increases in p8, Reg1/PSP, and PAP1/RegIII gene expression, mimicking the m olecular changes observed in pancreatic injury. By 12 m, Mist1(KO) mice dev elop lesions that contain cells coexpressing acinar and duct cell markers. Analysis of the factors involved in cholecystokinin (CCK) signaling reveal inappropriate levels of the CCK receptor A and the inositol-1,4,5-trisphosp hate receptor 3, suggesting that a functional defect exists in the regulate d exocytosis pathway of Mist1(KO) mice. Based on these observations, we pro pose that Mist1(KO) mice represent a new genetic model for chronic pancreas injury and that the Mist1 protein serves as a key regulator of acinar cell function, stability, and identity.