PMC7390928_01
PMC7390928_02
PMC7390928_03
PMC7390928_04
Laminin alpha2 in the ventricular-subventricular zone (VZ-SVZ) neural stem cell (NSC) niche. (A) Laminin alpha2 influences NSC proliferation and differentiation. It influences neurogenesis and gliogenesis in the VZ-SVZ, as well as the proliferation and survival of progenitors for midbrain dopaminergic neurons. (B) Oligodendrogenesis and myelination are influenced by LAMA2 expression. In particular, LAMA2 expression influences the survival and differentiation of oligodendrocyte precursor cells (OPCs) as well as the maturation of oligodendrocytes.
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F2
Functional roles of laminin alpha2 in other areas of the central nervous system (CNS). (A) Blood-brain barrier integrity is regulated by LAMA2 expression. Inset depicts laminin interaction with dystroglycan, which helps to cluster aquaporin-4 channels at barrier astrocytic endfeet. (B) Laminin alpha2 influences long-term synaptic plasticity. Inset depicts laminin interaction with dystroglycan, which helps to mediate the clustering of GABAA receptors at inhibitory synapses. (C) Neurite outgrowth and axon pathfinding are influenced by alpha2-containing laminins. Inset depicts laminin interaction with integrin alpha6beta1 in neuronal growth cones, which helps to couple extracellular matrix (ECM) and the actin cytoskeleton as growth cones extend.
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F3
Cortical dysplasia and NSC dysfunction in Congenital Muscular Dystrophies (CMD). Left: normal cortical development. Right: abnormal cortical development in CMD. 1. Breached BM caused by mutations in DAG1 and GPR56 genes, or abnormal glycosylation by fukutin, FKRP, and LARGE1. 2. Impaired oligodendrogenesis due to loss of LAMA2 and DAG1 expression or function. 3. The detachment of NSCs due to the loss of a functional interaction between laminin alpha2 and beta1 integrins. Inset: receptors mediate interactions between radial glial cell endfeet and with laminin alpha2: 1, Dystroglycan; 2, Integrin; 3, GPR56 and (possibly) GPR126. Abbreviations: BM, basement membrane; CP, cortical plate; IZ, intermediate zone; MZ/BM, Marginal Zone/Basement Membrane; NSC, neural stem cell; SVZ, subventricular zone; VZ, ventricular zone.
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F4
Neuronal migration defects are seen in several CMDs that result from mutations impairing dystroglycan function (Figure 4).
PMC7390928_05