Mist1 is necessary for the establishment of granule organization in serous exocrine cells of the gastrointestinal tract.
Establishing a pool of granules at the luminal border is a key step during exocrine cell development in the pancreas and is necessary for efficient release of digestive enzymes through regulated exocytosis. Several proteins have been linked to maintaining granule organization, but it is unclear which regulatory mechanisms are necessary to establish organization. Based on temporal and spatial expression, the transcription factor Mist1 is an excellent candidate, and analysis of mice that do not express Mist1 (Mist1KO) reveal disrupted cell morphology in adult pancreatic acini. To address Mist1's role in establishing granule location, we have characterized the organization of pancreatic acini throughout development in Mist1KO mice. Using various histological approaches, we have determined that correct granule organization is never established in pancreatic acini of Mist1KO mice. Further examination indicates that this disruption in granule targeting may be the primary defect in Mist1KO mice as granule organization is affected in other serous exocrine cells that normally express Mist1. To identify a mechanistic link between granule targeting and the loss of Mist1 function, intercellular junctions and the expression of Rab3D were assessed. While both of these factors are affected in Mist1KO mice, these changes alone do not account for the disorganization observed in Mist1KO tissues. Therefore, we conclude that Mist1 is necessary for complete differentiation and maturation of serous exocrine cells through the combined regulation of several exocrine specific genes.
Department of Physiology and Pharmacology, University of Western Ontario, Child Health Research Institute, London, Ont., Canada N6C 2V5.
Charis L
CL
Johnson
Agnes S
AS
Kowalik
Nagalingam
N
Rajakumar
Christopher L
CL
Pin
D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins; D005088:Exocrine Glands / Q000166:cytology / Q000196:embryology* / Q000254:growth & development*; D041981:Gastrointestinal Tract / Q000166:cytology / Q000196:embryology* / Q000254:growth & development*; D015870:Gene Expression; D015321:Gene Rearrangement; D007150:Immunohistochemistry; D051379:Mice; D008810:Mice, Inbred C57BL; D022142:Secretory Vesicles / Q000378:metabolism / Q000648:ultrastructure*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D020692:rab3 GTP-Binding Proteins / Q000378:metabolism
D051792:Basic Helix-Loop-Helix Proteins; D014157:Transcription Factors; D020692:rab3 GTP-Binding Proteins; C491312:Bhlha15 protein, mouse; C116711:Rab3d protein, mouse; C492133:Rab3d protein, rat