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 beta-catenin and Cdx function upstream of Math1, and lineage-specific genes such as Ngn3 act downstream of Gfi1.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Basic Helix-Loop-Helix Transcription Factors / genetics
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Basic Helix-Loop-Helix Transcription Factors / metabolism*
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Cell Differentiation / genetics*
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Cell Lineage / genetics*
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Crosses, Genetic
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DNA-Binding Proteins / genetics
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DNA-Binding Proteins / metabolism*
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Ear / embryology
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Goblet Cells / cytology
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Goblet Cells / metabolism
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Hematopoiesis / physiology
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Intestines / cytology
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Intestines / embryology*
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Lung / embryology
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Mice
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Mice, Mutant Strains
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Nerve Tissue Proteins / genetics
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Nerve Tissue Proteins / metabolism
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Neutropenia / genetics
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Neutropenia / metabolism
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Peyer's Patches / cytology
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Peyer's Patches / metabolism
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Transcription Factors / genetics
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Transcription Factors / metabolism*
Substances
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Atoh1 protein, mouse
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Basic Helix-Loop-Helix Transcription Factors
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DNA-Binding Proteins
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Gfi1 protein, mouse
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Nerve Tissue Proteins
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Neurog3 protein, mouse
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Transcription Factors