title: Fibroblast growth factor receptor 2c signaling is required for intestinal cell differentiation in zebrafish.
abstract: BACKGROUND
  There are four cell lineages derived from intestinal stem cells that are located at the crypt and villus in the mammalian intestine the non-secretory absorptive enterocytes, and the secretory cells, which include mucous-secreting goblet cells, regulatory peptide-secreting enteroendocrine cells and antimicrobial peptide-secreting Paneth cells. Although fibroblast growth factor (Fgf) signaling is important for cell proliferation and differentiation in various tissues, its role in intestinal differentiation is less well understood.
  
  
  RESULTS
  We used a loss of function approach to investigate the importance of Fgf signaling in intestinal cell differentiation in zebrafish; abnormal differentiation of goblet cells was observed when Fgf signaling was inhibited using SU5402 or in the Tg(hsp70ldnfgfr1-EGFP) transgenic line. We identified Fgfr2c as an important receptor for cell differentiation. The number of goblet cells and enteroendocrine cells was reduced in fgfr2c morphants. In addition to secretory cells, enterocyte differentiation was also disrupted in fgfr2c morphants. Furthermore, proliferating cells were increased in the morphants. Interestingly, the loss of fgfr2c expression repressed secretory cell differentiation and increased cell proliferation in the mib(ta52b) mutant that had defective Notch signaling.
  
  
  CONCLUSIONS
  In conclusion, we found that Fgfr2c signaling derived from mesenchymal cells is important for regulating the differentiation of zebrafish intestine epithelial cells by promoting cell cycle exit. The results of Fgfr2c knockdown in mib(ta52b) mutants indicated that Fgfr2c signaling is required for intestinal cell differentiation. These findings provide new evidences that Fgf signaling is required for the differentiation of intestinal cells in the zebrafish developing gut.
authors.affiliation: Institute of Medical Sciences, Tzu-Chi University, Hualien, Taiwan.
authors.forename: Da-Wei
authors.initials: DW
authors.lastname: Liu
authors.forename: Su-Mei
authors.initials: SM
authors.lastname: Tsai
authors.forename: Bih-Fen
authors.initials: BF
authors.lastname: Lin
authors.forename: Yun-Jin
authors.initials: YJ
authors.lastname: Jiang
authors.forename: Wen-Pin
authors.initials: WP
authors.lastname: Wang
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D001973:Bromodeoxyuridine; D002454:Cell Differentiation / Q000502:physiology*; D017931:DNA Primers / Q000235:genetics; D019858:Enteroendocrine Cells / Q000502:physiology; D005455:Fluorescent Antibody Technique; D020397:Goblet Cells / Q000502:physiology; D017403:In Situ Hybridization; D020287:In Situ Nick-End Labeling; D007422:Intestines / Q000166:cytology*; D008845:Microinjections; D060172:Morpholinos / Q000235:genetics; D011758:Pyrroles; D051497:Receptor, Fibroblast Growth Factor, Type 2 / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000502:physiology*; D015027:Zebrafish / Q000196:embryology*
chemical_list: D017931:DNA Primers; D060172:Morpholinos; D011758:Pyrroles; C105686:SU 5402; D051497:Receptor, Fibroblast Growth Factor, Type 2; D001973:Bromodeoxyuridine