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

NF Shroyer, D Wallis, KJT Venken… - Genes & …, 2005 - genesdev.cshlp.org
Genes & development, 2005genesdev.cshlp.org
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 …
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.
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