title: FGF9-Pitx2-FGF10 signaling controls cecal formation in mice.
abstract: Fibroblast growth factor (FGF) signaling to the epithelium and mesenchyme mediated by FGF10 and FGF9, respectively, controls cecal formation during embryonic development. In particular, mesenchymal FGF10 signals to the epithelium via FGFR2b to induce epithelial cecal progenitor cell proliferation. Yet the precise upstream mechanisms controlling mesenchymal FGF10 signaling are unknown. Complete deletion of Fgf9 as well as of Pitx2, a gene encoding a homeobox transcription factor, both lead to cecal agenesis. Herein, we used mouse genetic approaches to determine the precise contribution of the epithelium and/or mesenchyme tissue compartments in this process. Using tissue compartment specific Fgf9 versus Pitx2 loss of function approaches in the gut epithelium and/or mesenchyme, we determined that FGF9 signals to the mesenchyme via Pitx2 to induce mesenchymal Fgf10 expression, which in turn leads to epithelial cecal bud formation.
authors: Developmental Biology and Regenerative Medicine Program, Saban Research Institute of Children's Hospital Los Angeles, CA 90027, USA.
authors: Denise
authors: D
authors: Al Alam
authors: Frederic G
authors: FG
authors: Sala
authors: Sheryl
authors: S
authors: Baptista
authors: Rosanna
authors: R
authors: Galzote
authors: Soula
authors: S
authors: Danopoulos
authors: Caterina
authors: C
authors: Tiozzo
authors: Philip
authors: P
authors: Gage
authors: Tracy
authors: T
authors: Grikscheit
authors: David
authors: D
authors: Warburton
authors: Mark R
authors: MR
authors: Frey
authors: Saverio
authors: S
authors: Bellusci
mesh_terms: D000818:Animals; D001483:Base Sequence; D002432:Cecum / Q000002:abnormalities / Q000196:embryology* / Q000378:metabolism*; D049109:Cell Proliferation; D017931:DNA Primers / Q000235:genetics; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism; D005260:Female; D051526:Fibroblast Growth Factor 10 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D051525:Fibroblast Growth Factor 9 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008648:Mesoderm / Q000196:embryology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008817:Mice, Mutant Strains; D008822:Mice, Transgenic; D008954:Models, Biological; D011247:Pregnancy; D051497:Receptor, Fibroblast Growth Factor, Type 2 / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D014157:Transcription Factors / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D000097577:Homeobox Protein PITX2
chemical_list: D017931:DNA Primers; D051526:Fibroblast Growth Factor 10; D051525:Fibroblast Growth Factor 9; D018398:Homeodomain Proteins; D051497:Receptor, Fibroblast Growth Factor, Type 2; D014157:Transcription Factors; D000097577:Homeobox Protein PITX2; C496464:Fgf10 protein, mouse; C496460:Fgf9 protein, mouse