Dominant and context-specific control of endodermal organ allocation by Ptf1a.

Willet SG, Hale MA, Grapin-Botton A, Magnuson MA, MacDonald RJ, Wright CV
Development. 2014 141 (22): 4385-94

PMID: 25371369 · PMCID: PMC4302917 · DOI:10.1242/dev.114165

The timing and gene regulatory logic of organ-fate commitment from within the posterior foregut of the mammalian endoderm is largely unexplored. Transient misexpression of a presumed pancreatic-commitment transcription factor, Ptf1a, in embryonic mouse endoderm (Ptf1a(EDD)) dramatically expanded the pancreatic gene regulatory network within the foregut. Ptf1a(EDD) temporarily suppressed Sox2 broadly over the anterior endoderm. Pancreas-proximal organ territories underwent full tissue conversion. Early-stage Ptf1a(EDD) rapidly expanded the endogenous endodermal Pdx1-positive domain and recruited other pancreas-fate-instructive genes, thereby spatially enlarging the potential for pancreatic multipotency. Early Ptf1a(EDD) converted essentially the entire glandular stomach, rostral duodenum and extrahepatic biliary system to pancreas, with formation of many endocrine cell clusters of the type found in normal islets of Langerhans. Sliding the Ptf1a(EDD) expression window through embryogenesis revealed differential temporal competencies for stomach-pancreas respecification. The response to later-stage Ptf1a(EDD) changed radically towards unipotent, acinar-restricted conversion. We provide strong evidence, beyond previous Ptf1a inactivation or misexpression experiments in frog embryos, for spatiotemporally context-dependent activity of Ptf1a as a potent gain-of-function trigger of pro-pancreatic commitment.

© 2014. Published by The Company of Biologists Ltd.

MeSH Terms (13)

Animals Endoderm Fluorescent Antibody Technique Gastrointestinal Tract Gene Expression Regulation, Developmental Gene Regulatory Networks Histological Techniques Mice Microscopy, Confocal Organogenesis Pancreas SOXB1 Transcription Factors Transcription Factors

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