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Regulation of neurogenesis by Fgf8a requires Cdc42 signaling and a novel Cdc42 effector protein

Alissa M Hulstrand1, Douglas W Houston

  • 1Department of Biology and Interdisciplinary Graduate Program in Genetics, University of Iowa, Iowa City, IA 52242, USA.

Developmental Biology
|September 3, 2013
PubMed

Insights

Fibroblast growth factor 8a (Fgf8a) activates a novel Cdc42-dependent pathway. This pathway, involving Cdc42 effector protein 4-like (Cep4l), is crucial for sensory neurogenesis and neuronal development in vertebrates.

Area of Science:

  • Developmental Biology
  • Molecular Neuroscience
  • Cell Signaling

Background:

  • Fibroblast growth factor (FGF) signaling is vital for neural development, including neural induction, CNS patterning, and neurogenesis.
  • Ras/MAPK signaling is considered critical for FGF functions, but may not fully account for diverse FGF responses.

Purpose of the Study:

  • To investigate a novel Cdc42-dependent signaling pathway downstream of the Fgf8a splice isoform.
  • To elucidate the role of Cdc42 and its effector Cep4l in neuronal development and Fgf8a-mediated signaling.

Main Methods:

  • Characterization of a Cdc42-dependent pathway in Xenopus embryos.
  • Assessing the neuronal-inducing activity of Cdc42 effector 4-like protein (Cep4l).
  • In vivo analysis of Cdc42 and Cep4l function in sensory neurogenesis.

Main Results:

  • Cep4l exhibits robust neuronal-inducing activity in Xenopus embryos.
  • Cdc42 and Cep4l are both necessary and sufficient for sensory neurogenesis in vivo.
  • Fgf8a specifically promotes Cdc42/Cep4l association, unlike the non-neuronal inducing Fgf8b isoform.

Conclusions:

  • A novel Cdc42-dependent signaling pathway, involving Cep4l, is essential for Fgf8a-induced neuronal development.
  • This pathway plays a critical role in vertebrate sensory neurogenesis.
  • Fgf8a utilizes a specific signaling mechanism distinct from Fgf8b to drive neuronal induction.
Keywords:
Cdc42Cdc42 effector proteinFgf8NeurogenesisXenopus

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