Fibroblast growth factor 10 is required for survival and proliferation but not differentiation of intestinal epithelial progenitor cells during murine colon development.
Epithelial-mesenchymal interactions that govern the development of the colon from the primitive gastrointestinal tract are still unclear. In this study, we determine the temporal-spatial expression pattern of Fibroblast growth factor 10 (Fgf10), a key developmental gene, in the colon at different developmental stages. We found that Fgf10 is expressed in the mesenchyme of the distal colon, while its main receptor Fgfr2-IIIb is expressed throughout the entire intestinal epithelium. We demonstrate that Fgf10 inactivation leads to decreased proliferation and increased cell apoptosis in the colonic epithelium at E10.5, therefore resulting in distal colonic atresia. Using newly described Fgf10 hypomorphic mice, we show that high levels of FGF10 are dispensable for the differentiation of the colonic epithelium. Our work unravels for the first time the pivotal role of FGF10 in the survival and proliferation of the colonic epithelium, biological activities which are essential for colonic crypt formation.
Sala
Frédéric G
FG
UMR144-CNRS/Institut Curie, 75248 Paris cedex 05, France.
Curtis
Jennifer L
JL
Veltmaat
Jacqueline M
JM
Del Moral
Pierre-Marie
PM
Le
Lendy T
LT
Fairbanks
Timothy J
TJ
Warburton
David
D
Ford
Henri
H
Wang
Kasper
K
Burns
R Cartland
RC
Bellusci
Saverio
S
D000818:Animals; D002454:Cell Differentiation; D049109:Cell Proliferation; D002470:Cell Survival; D003106:Colon / Q000166:cytology / Q000196:embryology / Q000502:physiology*; D004847:Epithelial Cells / Q000166:cytology / Q000502:physiology*; D051526:Fibroblast Growth Factor 10 / Q000502:physiology*; D007413:Intestinal Mucosa / Q000166:cytology / Q000196:embryology / Q000502:physiology*; D008648:Mesoderm / Q000502:physiology; D051379:Mice; D051497:Receptor, Fibroblast Growth Factor, Type 2 / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology / Q000502:physiology*
C496464:Fgf10 protein, mouse; D051526:Fibroblast Growth Factor 10; D051497:Receptor, Fibroblast Growth Factor, Type 2