Impaired cortical neurogenesis in plexin-B1 and -B2 double deletion mutant.

Mammalian cortical expansion is tightly controlled by fine-tuning of proliferation and differentiation of neural progenitors in a region-specific manner. How extrinsic cues interface with cell-intrinsic programs to balance proliferative versus neurogenic decisions remains an unsolved question. We examined the function of Semaphorin receptors Plexin-B1 and -B2 in corticogenesis by generating double mutants, whereby Plexin-B2 was conditionally ablated in the developing brain in a Plexin-B1 null mutant background. Absence of both Plexin-Bs resulted in cortical thinning, particularly in the caudomedial cortex. Plexin-B1/B2 double, but not single, mutants exhibited a reduced neural progenitor pool, attributable to decreased proliferation and an altered division mode favoring cell cycle exit. This resulted in deficient production of neurons throughout the neurogenic period, proportionally affecting all cortical laminae. Consistent with the in vivo data, cultured neural progenitors lacking both Plexin-B1 and -B2 displayed decreased proliferative capacity and increased spontaneous differentiation. Our study therefore defines a novel function of Plexin-B1 and -B2 in transmitting extrinsic signals to maintain proliferative and undifferentiated states of neural progenitors. As single mutants displayed no apparent cortical defects, we conclude that Plexin-B1 and -B2 play redundant or compensatory roles during forebrain development to ensure proper neuronal production and neocortical expansion.