title: Regulation of neurogenesis by Fgf8a requires Cdc42 signaling and a novel Cdc42 effector protein.
abstract: Fibroblast growth factor (FGF) signaling is required for numerous aspects of neural development, including neural induction, CNS patterning and neurogenesis. The ability of FGFs to activate Ras/MAPK signaling is thought to be critical for these functions. However, it is unlikely that MAPK signaling can fully explain the diversity of responses to FGFs. We have characterized a Cdc42-dependent signaling pathway operating downstream of the Fgf8a splice isoform. We show that a Cdc42 effector 4-like protein (Cdc42ep4-l or Cep4l) has robust neuronal-inducing activity in Xenopus embryos. Furthermore, we find that Cep4l and Cdc42 itself are necessary and sufficient for sensory neurogenesis in vivo. Furthermore, both proteins are involved in Fgf8a-induced neuronal induction, and Cdc42/Cep4l association is promoted specifically by the Fgf8a isoform of Fgf8, but not by Fgf8b, which lacks neuronal inducing activity. Overall, these data suggest a novel role for Cdc42 in an Fgf8a-specific signaling pathway essential for vertebrate neuronal development.
authors.affiliation: Department of Biology and Interdisciplinary Graduate Program in Genetics, University of Iowa, Iowa City, IA 52242, USA.
authors.forename: Alissa M
authors.initials: AM
authors.lastname: Hulstrand
authors.forename: Douglas W
authors.initials: DW
authors.lastname: Houston
mesh_terms: D000818:Animals; D019521:Body Patterning / Q000235:genetics; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism; D004625:Embryo, Nonmammalian; D051524:Fibroblast Growth Factor 8 / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D055495:Neurogenesis / Q000235:genetics*; D015398:Signal Transduction; D014981:Xenopus; D029961:Zebrafish Proteins / Q000235:genetics* / Q000378:metabolism; D020764:cdc42 GTP-Binding Protein / Q000235:genetics* / Q000378:metabolism*
chemical_list: D002352:Carrier Proteins; C570455:Cdc42se1 protein, zebrafish; C496456:FGF8 protein, human; D029961:Zebrafish Proteins; D051524:Fibroblast Growth Factor 8; D020764:cdc42 GTP-Binding Protein
keywords: Cdc42; Cdc42 effector protein; Fgf8; Neurogenesis; Xenopus