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Here, Braun et al. investigated how cell cycle exit and synchronous differentiation onset are regulated in the embryonic brain, which is accompanied by BAF subunit switching to generate neuron-specific nBAF complexes in neural stem/progenitor cells. They manipulated the timing of BAF subunit exchange in vivo and found that early loss of the npBAF subunit BAF53a stalls cell cycle exit to disrupt neurogenesis and that Wnt, EGF, FGF, Sox2, myc, and Pax6 all fail to maintain proliferation in the absence of BAF53a, providing insight into a novel mechanism underlying neural progenitor cell cycle exit in the continued presence of extrinsic proliferative cues.

ABSTRACTThe blood-brain barrier (BBB) largely excludes antibodies from entering the central nervous system, thus limiting the potential of therapeutic antibodies to treat conditions such as neurodegenerative diseases and neuro-psychiatric disorders. Here, we demonstrate that the transport of human antibodies across the BBB in mice can be enhanced by modulating their interactions with the neonatal Fc receptor (FcRn). When M252Y/S254T/T246E substitutions are introduced on the antibody Fc domain, immunohistochemical assays reveal widespread distribution of the engineered antibodies throughout the mouse brain. These engineered antibodies remain specific for their antigens and retain pharmacological activity. We propose that novel brain-targeted therapeutic antibodies can be engineered to differentially engage FcRn for receptor-mediated transcytosis across the BBB in order to improve neurological disease therapeutics in the future.