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Neuron. 2015 Mar 4;85(5):998-1012. doi: 10.1016/j.neuron.2015.01.018.

Sip1 downstream Effector ninein controls neocortical axonal growth, ipsilateral branching, and microtubule growth and stability.

Author information

1
Institute for Cell and Neurobiology, Center for Anatomy, Charité-Universitätsmedizin Berlin, Virchowweg 6, 10117 Berlin, Germany; Max Planck Institute for Experimental Medicine, Hermann-Rein-Strasse 3, 37075 Göttingen, Germany.
2
Department of Physiology, Anatomy, and Genetics, Le Gros Clark Building, University of Oxford, Oxford OX1 3OX, UK.
3
Institute for Cell and Neurobiology, Center for Anatomy, Charité-Universitätsmedizin Berlin, Virchowweg 6, 10117 Berlin, Germany. Electronic address: victor.tarabykin@charite.de.

Abstract

Sip1 is an important transcription factor that regulates several aspects of CNS development. Mutations in the human SIP1 gene have been implicated in Mowat-Wilson syndrome (MWS), characterized by severe mental retardation and agenesis of the corpus callosum. In this study we have shown that Sip1 is essential for the formation of intracortical, intercortical, and cortico-subcortical connections in the murine forebrain. Sip1 deletion from all postmitotic neurons in the neocortex results in lack of corpus callosum, anterior commissure, and corticospinal tract formation. Mosaic deletion of Sip1 in the neocortex reveals defects in axonal growth and in ipsilateral intracortical-collateral formation. Sip1 mediates these effects through its direct downstream effector ninein, a microtubule binding protein. Ninein in turn influences the rate of axonal growth and branching by affecting microtubule stability and dynamics.

PMID:
25741725
DOI:
10.1016/j.neuron.2015.01.018
[Indexed for MEDLINE]
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