Laminin regulates postnatal oligodendrocyte production by promoting oligodendrocyte progenitor survival in the subventricular zone
Article first published online: 17 JUN 2012
Copyright © 2012 Wiley Periodicals, Inc.
Volume 60, Issue 10, pages 1451–1467, October 2012
How to Cite
Relucio, J., Menezes, M. J., Miyagoe-Suzuki, Y., Takeda, S. and Colognato, H. (2012), Laminin regulates postnatal oligodendrocyte production by promoting oligodendrocyte progenitor survival in the subventricular zone. Glia, 60: 1451–1467. doi: 10.1002/glia.22365
- Issue published online: 16 AUG 2012
- Article first published online: 17 JUN 2012
- Manuscript Accepted: 10 MAY 2012
- Manuscript Received: 19 MAY 2011
- National Institute of Neurological Disorders and Stroke. Grant Number: NS054042
- National Multiple Sclerosis Society. Grant Number: RG4357A2
- Empire State Stem Cell Fund (NY State Department of Health contract). Grant Number: CO26400
- oligodendrocyte progenitor cell;
- subventricular zone;
The laminin family of extracellular matrix proteins are expressed broadly during embryonic brain development, but are enriched at ventricular and pial surfaces where laminins mediate radial glial attachment during corticogenesis. In the adult brain, however, laminin distribution is restricted, yet is found within the vascular basal lamina and associated fractones of the ventricular zone (VZ)-subventricular zone (SVZ) stem cell niche, where laminins regulate adult neural progenitor cell proliferation. It remains unknown, however, if laminins regulate the wave of oligodendrogenesis that occurs in the neonatal/early postnatal VZ-SVZ. Here we report that Lama2, the gene that encodes the laminin α2-subunit, regulates postnatal oligodendrogenesis. At birth, Lama2−/− mice had significantly higher levels of dying oligodendrocyte progenitor cells (OPCs) in the OPC germinal zone of the dorsal SVZ. This translated into fewer OPCs, both in the dorsal SVZ well as in an adjacent developing white matter tract, the corpus callosum. In addition, intermediate progenitor cells that give rise to OPCs in the Lama2−/− VZ-SVZ were mislocalized and proliferated nearer to the ventricle surface. Later, delays in oligodendrocyte maturation (with accompanying OPC accumulation), were observed in the Lama2−/− corpus callosum, leading to dysmyelination by postnatal day 21. Together these data suggest that prosurvival laminin interactions in the developing postnatal VZ-SVZ germinal zone regulate the ability, or timing, of oligodendrocyte production to occur appropriately. © 2012 Wiley Periodicals, Inc.