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

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.

• Authors: Swathi Srivatsa, Srinivas Parthasarathy, Zoltán Molnár, Victor Tarabykin
• Journal: Neuron (Neuron) Vol. 85 Issue 5 Pg. 998-1012 (Mar 04 2015) ISSN: 1097-4199 [Electronic] United States
• PMID: 25741725 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 Elsevier Inc. All rights reserved.

Chemical References

• Cytoskeletal Proteins
• Nerve Tissue Proteins
• Nin protein, mouse
• Nuclear Proteins
• Sip1 protein, mouse

Topics

• Animals
• Axons (physiology)
• Cells, Cultured
• Corpus Callosum (cytology, metabolism)
• Cytoskeletal Proteins (physiology)
• HEK293 Cells
• Humans
• Mice
• Mice, Transgenic
• Microtubules (physiology)
• Neocortex (cytology, metabolism)
• Nerve Tissue Proteins (deficiency, genetics)
• Nuclear Proteins (physiology)
• Prosencephalon (cytology, metabolism)