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

Spencer G. Willet, Michael A. Hale, Anne Grapin-Botton, Mark A. Magnuson, Raymond J. MacDonald, Christopher V E Wright

Research output: Contribution to journalArticle

15 Scopus citations

Abstract

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 pancreaticcommitment transcription factor, Ptf1a, in embryonic mouse endoderm (Ptf1aEDD) dramatically expanded the pancreatic gene regulatory network within the foregut. Ptf1aEDD temporarily suppressed Sox2 broadly over the anterior endoderm. Pancreas-proximal organ territories underwent full tissue conversion. Early-stage Ptf1aEDD rapidly expanded the endogenous endodermal Pdx1-positive domain and recruited other pancreas-fate-instructive genes, thereby spatially enlarging the potential for pancreatic multipotency. Early Ptf1aEDD converted essentially the entire glandular stomach, rostral duodenum and extrahepatic biliary systemto pancreas,with formation of manyendocrine cell clusters of the type found in normal islets of Langerhans. Sliding the Ptf1aEDD expression window through embryogenesis revealed differential temporal competencies for stomach-pancreas respecification. The response to later-stage Ptf1aEDD 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.

Original languageEnglish (US)
Pages (from-to)4385-4394
Number of pages10
JournalDevelopment (Cambridge)
Volume141
Issue number22
DOIs
StatePublished - Nov 1 2014

Keywords

  • Glandular stomach
  • Mouse
  • Pancreas
  • Pdx1
  • Ptf1a
  • Respecification

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology

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    Willet, S. G., Hale, M. A., Grapin-Botton, A., Magnuson, M. A., MacDonald, R. J., & Wright, C. V. E. (2014). Dominant and context-specific control of endodermal organ allocation by Ptf1a. Development (Cambridge), 141(22), 4385-4394. https://doi.org/10.1242/dev.114165