Phosphorylation of neurogenin2 specifies the migration properties and the dendritic morphology of pyramidal neurons in the neocortex

Randal Hand, Dante Bortone, Pierre Mattar, Laurent Nguyen, Julian Ik Tsen Heng, Sabrice Guerrier, Elizabeth Boutt, Eldon Peters, Anthony P. Barnes, Carlos Parras, Carol Schuurmans, François Guillemot, Franck Polleux

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Abstract

The molecular mechanisms specifying the dendritic morphology of different neuronal subtypes are poorly understood. Here we demonstrate that the bHLH transcription factor Neurogenin2 (Ngn2) is both necessary and sufficient for specifying the dendritic morphology of pyramidal neurons in vivo by specifying the polarity of its leading process during the initiation of radial migration. The ability of Ngn2 to promote a polarized leading process outgrowth requires the phosphorylation of a single tyrosine residue at position 241, an event that is neither involved in Ngn2 direct transactivation properties nor its proneural function. Interestingly, the migration defect observed in the Ngn2 knockout mouse and in progenitors expressing the Ngn2Y241F mutation can be rescued by inhibiting the activity of the small-GTPase RhoA in cortical progenitors. Our results demonstrate that Ngn2 coordinates the acquisition of the radial migration properties and the unipolar dendritic morphology characterizing pyramidal neurons through molecular mechanisms distinct from those mediating its proneural activity.

Original languageEnglish (US)
Pages (from-to)45-62
Number of pages18
JournalNeuron
Volume48
Issue number1
DOIs
StatePublished - Oct 6 2005

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ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Hand, R., Bortone, D., Mattar, P., Nguyen, L., Heng, J. I. T., Guerrier, S., Boutt, E., Peters, E., Barnes, A. P., Parras, C., Schuurmans, C., Guillemot, F., & Polleux, F. (2005). Phosphorylation of neurogenin2 specifies the migration properties and the dendritic morphology of pyramidal neurons in the neocortex. Neuron, 48(1), 45-62. https://doi.org/10.1016/j.neuron.2005.08.032