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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 .

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