title: A combination of Wnt and growth factor signaling induces Arl4c expression to form epithelial tubular structures.
abstract: Growth factor-dependent epithelial morphological changes and proliferation are essential for the formation of tubular structures, but the underlying molecular mechanisms are poorly understood. Co-stimulation with Wnt3a and epidermal growth factor (Wnt3a/EGF) induced development of tubes consisting of intestinal epithelial cells by inducing expression of Arl4c, an Arf-like small GTP-binding protein, in three-dimensional culture, while stimulation with Wnt3a or EGF alone did not. Arl4c expression resulted in rearrangement of the cytoskeleton through activation of Rac and inactivation of Rho properly, which promoted cell growth by inducing nuclear translocation of Yes-associated protein and transcriptional co-activator with PDZ-binding motif (YAP/TAZ) in leading cells. Arl4c was expressed in ureteric bud tips and pretubular structures in the embryonic kidney. In an organoid culture assay, Wnt and fibroblast growth factor signaling simultaneously induced elongation and budding of kidney ureteric buds through Arl4c expression. YAP/TAZ was observed in the nucleus of extending ureteric bud tips. Thus, Arl4c expression induced by a combination of growth factor signaling mechanisms is involved in tube formation.
authors.affiliation: Department of Molecular Biology and Biochemistry, Graduate School of Medicine Osaka University, Osaka, Japan.
authors.forename: Shinji
authors.initials: S
authors.lastname: Matsumoto
authors.forename: Shinsuke
authors.initials: S
authors.lastname: Fujii
authors.forename: Akira
authors.initials: A
authors.lastname: Sato
authors.forename: Souji
authors.initials: S
authors.lastname: Ibuka
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Kagawa
authors.forename: Masaru
authors.initials: M
authors.lastname: Ishii
authors.forename: Akira
authors.initials: A
authors.lastname: Kikuchi
mesh_terms: D020727:ADP-Ribosylation Factors / Q000378:metabolism*; D000217:Acyltransferases; D000818:Animals; D002448:Cell Adhesion; D002454:Cell Differentiation; D002478:Cells, Cultured; D003599:Cytoskeleton / Q000378:metabolism; D004285:Dogs; D004815:Epidermal Growth Factor / Q000378:metabolism*; D004847:Epithelial Cells / Q000166:cytology / Q000502:physiology; D005260:Female; D005333:Fetus; D005346:Fibroblast Growth Factors / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000166:cytology; D007668:Kidney / Q000196:embryology; D061985:Madin Darby Canine Kidney Cells; D051379:Mice; D008810:Mice, Inbred C57BL; D051381:Rats; D015398:Signal Transduction; D014157:Transcription Factors / Q000378:metabolism*; D060508:Wnt3 Protein / Q000378:metabolism*
chemical_list: D014157:Transcription Factors; D060508:Wnt3 Protein; C555509:Wnt3 protein, rat; D005346:Fibroblast Growth Factors; D004815:Epidermal Growth Factor; D000217:Acyltransferases; C544439:Tafazzin protein, rat; C486430:Arl4a protein, rat; D020727:ADP-Ribosylation Factors