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Dev Biol 2013 Oct 15;3822:385-99. doi: 10.1016/j.ydbio.2013.08.020.
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Regulation of neurogenesis by Fgf8a requires Cdc42 signaling and a novel Cdc42 effector protein.

Hulstrand AM , Houston DW .

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.

PubMed ID: 23994638
PMC ID: PMC3846544
Article link: Dev Biol
Grant support: [+]

Species referenced: Xenopus
Genes referenced: ccdc24 cdc42 cdc42ep4 crocc egr2 elavl1 fgf4 fgf8 foxi1 gal.2 hoxb9 hoxc9-like isl1 krt12.4 mapk1 mrc1 neurod1 neurog2 nog nrp1 odc1 pax2 pax6 rac1 rho runx1 snai1 sox2 sox9 tubb2b XB5748694
Antibodies: Ctnnb1 Ab6 FLAG Ab1 HA Ab4 Mapk1 Ab1 Neuronal Ab1 Tubb Ab1
Morpholinos: cdc42 MO1 cep4l MO1

Article Images: [+] show captions
References [+] :
Ash, Genetic analysis of the interface between Cdc42p and the CRIB domain of Ste20p in Saccharomyces cerevisiae. 2003, Pubmed