Laminin regulates postnatal oligodendrocyte production by promoting oligodendrocyte progenitor survival in the 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.
Department of Pharmacology, Stony Brook University, Stony Brook, New York, 11794, USA.
Jenne
J
Relucio
Michael J
MJ
Menezes
Yuko
Y
Miyagoe-Suzuki
Shin'ichi
S
Takeda
Holly
H
Colognato
D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D000941:Antigens / Q000378:metabolism; D002454:Cell Differentiation / Q000502:physiology*; D049109:Cell Proliferation; D002470:Cell Survival / Q000235:genetics; D002552:Cerebral Ventricles / Q000166:cytology*; D005136:Eye Proteins / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental / Q000235:genetics*; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D018398:Homeodomain Proteins / Q000378:metabolism; D020287:In Situ Nick-End Labeling; D007797:Laminin / Q000172:deficiency / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D046529:Microscopy, Electron, Transmission; D009413:Nerve Fibers, Myelinated / Q000502:physiology; D009836:Oligodendroglia / Q000502:physiology* / Q000648:ultrastructure; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors / Q000378:metabolism; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D011509:Proteoglycans / Q000378:metabolism; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000378:metabolism; D012097:Repressor Proteins / Q000378:metabolism; D055748:SOXB1 Transcription Factors / Q000235:genetics; D013234:Stem Cells / Q000502:physiology* / Q000648:ultrastructure; D000099216:Chondroitin Sulfate Proteoglycan 4
D000941:Antigens; D005136:Eye Proteins; D005904:Glial Fibrillary Acidic Protein; D018398:Homeodomain Proteins; D007797:Laminin; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors; D018809:Proliferating Cell Nuclear Antigen; D011509:Proteoglycans; D020796:Receptor, Platelet-Derived Growth Factor alpha; D012097:Repressor Proteins; D055748:SOXB1 Transcription Factors; D000099216:Chondroitin Sulfate Proteoglycan 4; C000605732:Pax6 protein, mouse; C527783:Sox2 protein, mouse; C102645:laminin alpha 2