Gfi1 functions downstream of Math1 to control intestinal secretory cell subtype allocation and differentiation.
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.
Shroyer
Noah F
NF
Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas 77030, USA.
Wallis
Deeann
D
Venken
Koen J T
KJ
Bellen
Hugo J
HJ
Zoghbi
Huda Y
HY
D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation / Q000235:genetics*; D019070:Cell Lineage / Q000235:genetics*; D003433:Crosses, Genetic; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D004423:Ear / Q000196:embryology; D020397:Goblet Cells / Q000166:cytology / Q000378:metabolism; D006410:Hematopoiesis / Q000502:physiology; D007422:Intestines / Q000166:cytology / Q000196:embryology*; D008168:Lung / Q000196:embryology; D051379:Mice; D008817:Mice, Mutant Strains; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D009503:Neutropenia / Q000235:genetics / Q000378:metabolism; D010581:Peyer's Patches / Q000166:cytology / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
D051792:Basic Helix-Loop-Helix Proteins; D004268:DNA-Binding Proteins; D009419:Nerve Tissue Proteins; D014157:Transcription Factors; C500943:Atoh1 protein, mouse; C079873:Gfi1 protein, mouse; C407737:Neurog3 protein, mouse