Review

Rev Diabet Stud, 2014, 11(1):51-83 DOI 10.1900/RDS.2014.11.51

Sox9: A Master Regulator of the Pancreatic Program

Philip A. Seymour

The Danish Stem Cell Center (DanStem), University of Copenhagen, Panum Institute, Blegdamsvej 3B, DK-2200, Copenhagen N, Denmark

Manuscript submitted July 26, 2013; resubmitted August 9, 2013; accepted August 10, 2013.

Keywords: Sox9, pancreas development, beta-cell, multipotent progenitor cell, Fgf, Pdx1, Notch, Hes1, transgenic mouse, molecular marker

Abstract

Over the last decade, it has been discovered that the transcription factor Sox9 plays several critical roles in governing the development of the embryonic pancreas and the homeostasis of the mature organ. While analysis of pancreata from patients affected by the Sox9 haploinsufficiency syndrome campomelic dysplasia initially alluded to a functional role of Sox9 in pancreatic morphogenesis, transgenic mouse models have been instrumental in mechanistically dissecting such roles. Although initially defined as a marker and maintenance factor for pancreatic progenitors, Sox9 is now considered to fulfill additional indispensable functions during pancreogenesis and in the postnatal organ through its interactions with other transcription factors and signaling pathways such as Fgf and Notch. In addition to maintaining both multipotent and bipotent pancreatic progenitors, Sox9 is also required for initiating endocrine differentiation and maintaining pancreatic ductal identity, and it has recently been unveiled as a key player in the initiation of pancreatic cancer. These functions of Sox9 are discussed in this article, with special emphasis on the knowledge gained from various loss-of-function and lineage tracing mouse models. Also, current controversies regarding Sox9 function in healthy and injured adult pancreas and unanswered questions and avenues of future study are discussed.

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