14-3-3ε and ζ regulate neurogenesis and differentiation of neuronal progenitor cells in the developing brain

Kazuhito Toyo-Oka, Tomoka Wachi, Robert F. Hunt, Scott C. Baraban, Shinichiro Taya, Hayley Ramshaw, Kozo Kaibuchi, Quenten P. Schwarz, Angel F. Lopez, Anthony Wynshaw-Boris

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47 Citations (Scopus)

Abstract

During brain development, neural progenitor cells proliferate and differentiate into neural precursors. These neural precursors migrate along the radial glial processes and localize at their final destination in the cortex. Numerous reports have revealed that 14-3-3 proteins are involved in many neuronal activities, although their functions in neurogenesis remain unclear. Here, using 14-3-3ε/ζ double knockout mice, we found that 14-3-3 proteins are important for proliferation and differentiation of neural progenitor cells in the cortex, resulting in neuronal migration defects and seizures. 14-3-3 deficiency resulted in the increase of δ-catenin and the decrease of β-catenin andαN-catenin. 14-3-3 proteins regulated neuronal differentiation into neurons via direct interactions with phosphorylated α-catenin to promote F-actin formation through a catenin/Rho GTPase/Limk1/cofilin signaling pathway. Conversely, neuronal migration defects seen in the double knock-out mice were restored by phosphomimic Ndel1 mutants, but notδ-catenin. Our findings provide new evidence that 14-3-3 proteins play important roles in neurogenesis and neuronal migration via the regulation of distinct signaling cascades.

Original languageEnglish
Pages (from-to)12168-12181
Number of pages14
JournalJournal of Neuroscience
Volume34
Issue number36
DOIs
Publication statusPublished - 03-09-2014

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)

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    Toyo-Oka, K., Wachi, T., Hunt, R. F., Baraban, S. C., Taya, S., Ramshaw, H., Kaibuchi, K., Schwarz, Q. P., Lopez, A. F., & Wynshaw-Boris, A. (2014). 14-3-3ε and ζ regulate neurogenesis and differentiation of neuronal progenitor cells in the developing brain. Journal of Neuroscience, 34(36), 12168-12181. https://doi.org/10.1523/JNEUROSCI.2513-13.2014