β2 and γ3 laminins are critical cortical basement membrane components ablation of Lamb2 and Lamc3 genes disrupt cortical lamination and produces dysplasia

Here, the authors demonstrate the significance of laminin b2 and g3 expression in maintaining a functional cortical pial basement membrane to which Cajal Retzius and radial glial cells attach and in turn guide neural development. Several isoforms of laminins, those containing b2 and g3 in particular, have been isolated from the brain underlining their importance in CNS functions. In the present study, the authors employ a reverse genetic approach where mice with a homozygous deletion of b2 and g3 genes displayed cortical laminar disorganization. In addition, the ablation of both these laminin chains resulted in the incidence of human cobblestone lissencephaly. Interestingly, heterozygous mice also exhibited disruption of cortical neurons with lesser severity. In fact, similar to b2 distribution, g3 was also observed to be localized in the developing cortex. Mutation in the binding site of the laminin g1 gene results in abnormal cortex lamination.