Gfi1 functions downstream of Math1 to control intestinal secretory cell subtype allocation and differentiation

  1. Noah F. Shroyer1,2,
  2. Deeann Wallis1,3,6,
  3. Koen J.T. Venken4,
  4. Hugo J. Bellen1,3,4,5, and
  5. Huda Y. Zoghbi1,2,3,4,5,7
  1. Departments of 1Molecular and Human Genetics, 2Pediatrics, and 5Neuroscience, 3Howard Hughes Medical Institute, 4Program in Developmental Biology, Baylor College of Medicine, Houston, Texas 77030, USA

Abstract

Gfi1 is a transcriptional repressor implicated in lymphomagenesis, neutropenia, and hematopoietic development, as well as ear and lung development. Here, we demonstrate that Gfi1 functions downstream of Math1 in intestinal secretory lineage differentiation. Gfi1-/- mice lack Paneth cells, have fewer goblet cells, and supernumerary enteroendocrine cells. Gfi1-/- mice show gene expression changes consistent with this altered cell allocation. These data suggest that Gfi1 functions to select goblet/Paneth versus enteroendocrine progenitors. We propose a model of intestinal cell fate choice in which β-catenin and Cdx function upstream of Math1, and lineage-specific genes such as Ngn3 act downstream of Gfi1.

Keywords

Footnotes

  • Supplemental material is available at http://www.genesdev.org.

  • Article and publication are at http://www.genesdev.org/cgi/doi/10.1101/gad.1353905.

  • 6 Present address: Deeann Wallis Schultz, National Human Genome Research Institute-Contractor, National Institutes of Health, 35 Convent Drive-MSC 3717, Building 35, Room 1B-407, Bethesda, MD 20892-3717, USA.

  • 7 Corresponding author.

    7 E-MAIL hzoghbi{at}bcm.tmc.edu; FAX (713) 798-8728.

    • Accepted August 8, 2005.
    • Received July 11, 2005.
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