Format

Send to

Choose Destination
Cell Rep. 2015 Oct 13;13(2):326-36. doi: 10.1016/j.celrep.2015.08.082. Epub 2015 Oct 1.

A Gene Regulatory Network Cooperatively Controlled by Pdx1 and Sox9 Governs Lineage Allocation of Foregut Progenitor Cells.

Author information

1
Departments of Pediatrics and Cellular & Molecular Medicine, Pediatric Diabetes Research Center, University of California San Diego, La Jolla, CA 92093, USA.
2
Departments of Pediatrics and Cellular & Molecular Medicine, Pediatric Diabetes Research Center, University of California San Diego, La Jolla, CA 92093, USA; DanStem, University of Copenhagen, Blegdamsvej 3B, DK-2200, Copenhagen N, Denmark.
3
Department of Cellular & Molecular Medicine, University of California San Diego, La Jolla, CA 92093, USA.
4
Center for Stem Cell Biology, Vanderbilt University, 2213 Garland Avenue, Nashville, TN 37232, USA.
5
Departments of Pediatrics and Cellular & Molecular Medicine, Pediatric Diabetes Research Center, University of California San Diego, La Jolla, CA 92093, USA. Electronic address: masander@ucsd.edu.

Abstract

The generation of pancreas, liver, and intestine from a common pool of progenitors in the foregut endoderm requires the establishment of organ boundaries. How dorsal foregut progenitors activate pancreatic genes and evade the intestinal lineage choice remains unclear. Here, we identify Pdx1 and Sox9 as cooperative inducers of a gene regulatory network that distinguishes the pancreatic from the intestinal lineage. Genetic studies demonstrate dual and cooperative functions for Pdx1 and Sox9 in pancreatic lineage induction and repression of the intestinal lineage choice. Pdx1 and Sox9 bind to regulatory sequences near pancreatic and intestinal differentiation genes and jointly regulate their expression, revealing direct cooperative roles for Pdx1 and Sox9 in gene activation and repression. Our study identifies Pdx1 and Sox9 as important regulators of a transcription factor network that initiates pancreatic fate and sheds light on the gene regulatory circuitry that governs the development of distinct organs from multi-lineage-competent foregut progenitors.

PMID:
26440894
PMCID:
PMC4607666
DOI:
10.1016/j.celrep.2015.08.082
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center