title: FGF is essential for both condensation and mesenchymal-epithelial transition stages of pronephric kidney tubule development.
abstract: The pronephros is a transient embryonic kidney that is essential for the survival of aquatic larvae. It is also absolutely critical for adult kidney development, as the pronephric derivative the wolffian duct forms the ductal system of the adult kidney and also triggers the condensation of metanephric mesenchyme into the adult nephrons. While exploring Xenopus pronephric patterning, we observed that epidermally delivered hedgehog completely suppresses pronephric kidney tubule development but does not effect development of the pronephric glomus, the equivalent of the mammalian glomerulus or corpuscle. This effect is not mediated by apoptosis. Microarray analysis of microdissected primordia identified FGF8 as one of the potential mediators of hedgehog action. Further investigation demonstrated that SU5402-sensitive FGF signaling plays a critical role in the very earliest stages of pronephric tubule development. Modulation of FGF8 activity using a morpholino has a later effect that blocks condensation of pronephric mesenchyme into the pronephric tubule. Together, these data show that FGF signaling plays a critical role at two stages of embryonic kidney development, one in the condensation of the pronephric primordium from the intermediate mesoderm and a second in the later epithelialization of this mesenchyme into the pronephric nephron. The data also show that in Xenopus, development of the glomus/glomerulus can be uncoupled from nephron formation via ectopic hedgehog expression and provides an experimental avenue for investigating glomerulogenesis in the complete absence of tubules.
authors.affiliation: Department of Biological Science, University of Calgary, 2500 University Drive NW, Calgary, Alberta, Canada T2N 1N4.
authors.forename: Anna E
authors.initials: AE
authors.lastname: Urban
authors.forename: Xiaolan
authors.initials: X
authors.lastname: Zhou
authors.forename: Josette M
authors.initials: JM
authors.lastname: Ungos
authors.forename: David W
authors.initials: DW
authors.lastname: Raible
authors.forename: Curtis R
authors.initials: CR
authors.lastname: Altmann
authors.forename: Peter D
authors.initials: PD
authors.lastname: Vize
mesh_terms: D000818:Animals; D019521:Body Patterning / Q000502:physiology; D004625:Embryo, Nonmammalian; D004627:Embryonic Induction; D004847:Epithelial Cells / Q000502:physiology; D051524:Fibroblast Growth Factor 8 / Q000235:genetics / Q000378:metabolism; D005346:Fibroblast Growth Factors / Q000502:physiology*; D018507:Gene Expression Regulation, Developmental; D053823:Hedgehog Proteins; D007668:Kidney / Q000166:cytology* / Q000196:embryology*; D008648:Mesoderm / Q000502:physiology*; D009399:Nephrons / Q000196:embryology; D020411:Oligonucleotide Array Sequence Analysis; D011758:Pyrroles / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism; D029867:Xenopus Proteins / Q000235:genetics / Q000378:metabolism; D014982:Xenopus laevis / Q000196:embryology*
chemical_list: C496457:Fgf8 protein, mouse; D053823:Hedgehog Proteins; D011758:Pyrroles; C105686:SU 5402; D015534:Trans-Activators; D029867:Xenopus Proteins; D051524:Fibroblast Growth Factor 8; D005346:Fibroblast Growth Factors