Fibroblast Growth Factor Receptor 2c Signaling Is Required for Intestinal Cell Differentiation in Zebrafish

Abstract

BackgroundThere 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.Methodology/Principal FindingsWe 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 mibta52b mutant that had defective Notch signaling.Conclusions/SignificanceIn 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 mibta52b 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.

Transcriptomic and proteomic signatures of stemness and differentiation in the colon crypt

“…These patterns are consistent with knockout phenotypes in the intestine. For example, Fgfr3-knockout mice display enhanced proliferation in the TAZ 73 , and knockout of Fgfr2c in zebrafish leads to a loss of goblet and EEC 74 . UPR is most active in the secretory lineage ( Fig.…”

Regional environmental pressure influences population differentiation in turbot (Scophthalmus maximus)

“…FGF receptors are involved in many biological processes during embryo development and the adult stage, including morphogenesis, cell proliferation and lipid metabolism, all related to some degree with growth (Groth & Lardelli ; Liu et al . ). As such, a significant association for this markers with growth‐related traits was found by Sánchez‐Molano et al .…”

Overexpression of miR-595 and miR-1246 in the Sera of Patients with Active Forms of Inflammatory Bowel Disease

“…[41][42][43] Gene knockout mice deficient in IIIb splice variants of FGFR1 and FGFR2 in keratinocytes suffer from a loss of FGF-induced expression of TJ components with subsequent deficits in epidermal barrier function, which induces an inflammatory response. 44 FGFR2 signaling is required for differentiation of intestinal cells in zebrafish, 45 airway branching and epithelial differentiation of mouse lung, 46 and for cecal development in mice. 47 Loss of FGFR2b is responsible for intestinal atresia.…”