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Title page for ETD etd-10092014-130733

Type of Document Dissertation
Author Willet, Spencer Gaffney
URN etd-10092014-130733
Title Dominant and Context-Specific Control of Endodermal Organ Allocation by Ptf1a
Degree PhD
Department Cell and Developmental Biology
Advisory Committee
Advisor Name Title
Roland Stein Committee Chair
Christopher V.E. Wright Committee Member
Guoqiang Gu Committee Member
Michelle Southard-Smith Committee Member
  • Pancreas
  • Ptf1a
  • Stomach
  • Pdx1
Date of Defense 2014-09-23
Availability unrestricted

Dominant and Context-Specific Control of Endodermal

Organ Allocation by Ptf1a

Spencer Gaffney Willet

Dissertation under the direction of Professor Christopher V.E. Wright

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 (Ptf1aEDD) dramatically expanded the pancreatic gene regulatory network within the foregut. 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 system to pancreas. 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.

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