Dominant and Context-Specific Control of Endodermal Organ Allocation by Ptf1a

Abstract

CELL AND DEVELOPMENTAL BIOLOGY

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.