TGF-β Signaling Specifies Axons during Brain Development

Jason J. Yi, Anthony P. Barnes, Randal Hand, Franck Polleux, Michael D. Ehlers

Research output: Contribution to journalArticle

161 Scopus citations

Abstract

In the mammalian brain, the specification of a single axon and multiple dendrites occurs early in the differentiation of most neuron types. Numerous intracellular signaling events for axon specification have been described in detail. However, the identity of the extracellular factor(s) that initiate neuronal polarity in vivo is unknown. Here, we report that transforming growth factor β (TGF-β) initiates signaling pathways both in vivo and in vitro to fate naive neurites into axons. Neocortical neurons lacking the type II TGF-β receptor (TβR2) fail to initiate axons during development. Exogenous TGF-β is sufficient to direct the rapid growth and differentiation of an axon, and genetic enhancement of receptor activity promotes the formation of multiple axons. Finally, we show that the bulk of these TGF-β-dependent events are mediated by site-specific phosphorylation of Par6. These results define an extrinsic cue for neuronal polarity in vivo that patterns neural circuits in the developing brain.

Original languageEnglish (US)
Pages (from-to)144-157
Number of pages14
JournalCell
Volume142
Issue number1
DOIs
StatePublished - Jul 1 2010

Keywords

  • Molneuro

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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  • Cite this

    Yi, J. J., Barnes, A. P., Hand, R., Polleux, F., & Ehlers, M. D. (2010). TGF-β Signaling Specifies Axons during Brain Development. Cell, 142(1), 144-157. https://doi.org/10.1016/j.cell.2010.06.010