| First Author | Pawlisz AS | Year | 2011 |
| Journal | PLoS Biol | Volume | 9 |
| Issue | 10 | Pages | e1001172 |
| PubMed ID | 22028625 | Mgi Jnum | J:184033 |
| Mgi Id | MGI:5319752 | Doi | 10.1371/journal.pbio.1001172 |
| Citation | Pawlisz AS, et al. (2011) Three-dimensional regulation of radial glial functions by Lis1-Nde1 and dystrophin glycoprotein complexes. PLoS Biol 9(10):e1001172 |
| abstractText | Radial glial cells (RGCs) are distinctive neural stem cells with an extraordinary slender bipolar morphology and dual functions as precursors and migration scaffolds for cortical neurons. Here we show a novel mechanism by which the Lis1-Nde1 complex maintains RGC functions through stabilizing the dystrophin/dystroglycan glycoprotein complex (DGC). A direct interaction between Nde1 and utrophin/dystrophin allows for the assembly of a multi-protein complex that links the cytoskeleton to the extracellular matrix of RGCs to stabilize their lateral membrane, cell-cell adhesion, and radial morphology. Lis1-Nde1 mutations destabilized the DGC and resulted in deformed, disjointed RGCs and disrupted basal lamina. Besides impaired RGC self-renewal and neuronal migration arrests, Lis1-Nde1 deficiencies also led to neuronal over-migration. Additional to phenotypic resemblances of Lis1-Nde1 with DGC, strong synergistic interactions were found between Nde1 and dystroglycan in RGCs. As functional insufficiencies of LIS1, NDE1, and dystroglycan all cause lissencephaly syndromes, our data demonstrated that a three-dimensional regulation of RGC's cytoarchitecture by the Lis1-Nde1-DGC complex determines the number and spatial organization of cortical neurons as well as the size and shape of the cerebral cortex. |
