RESUMO
Polarized, non-overlapping, regularly spaced, tiled organization of radial glial cells (RGCs) serves as a framework to generate and organize cortical neuronal columns, layers, and circuitry. Here, we show that mediator of cell motility 1 (Memo1) is a critical determinant of radial glial tiling during neocortical development. Memo1 deletion or knockdown leads to hyperbranching of RGC basal processes and disrupted RGC tiling, resulting in aberrant radial unit assembly and neuronal layering. Memo1 regulates microtubule (MT) stability necessary for RGC tiling. Memo1 deficiency leads to disrupted MT minus-end CAMSAP2 distribution, initiation of aberrant MT branching, and altered polarized trafficking of key basal domain proteins such as GPR56, and thus aberrant RGC tiling. These findings identify Memo1 as a mediator of RGC scaffold tiling, necessary to generate and organize neurons into functional ensembles in the developing cerebral cortex.
Assuntos
Células Ependimogliais/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/genética , Neocórtex/embriologia , Células-Tronco Neurais/metabolismo , Neurônios/metabolismo , Animais , Transtorno Autístico/genética , Movimento Celular/genética , Polaridade Celular , Cerebelo/embriologia , Córtex Cerebral/citologia , Córtex Cerebral/embriologia , Córtex Cerebral/metabolismo , Células Ependimogliais/citologia , Técnicas de Silenciamento de Genes , Células HEK293 , Hipocampo/embriologia , Humanos , Camundongos , Proteínas Associadas aos Microtúbulos/metabolismo , Microtúbulos/metabolismo , Neocórtex/citologia , Neocórtex/metabolismo , Células-Tronco Neurais/citologia , Neurônios/citologia , Transporte Proteico , Receptores Acoplados a Proteínas G/metabolismoRESUMO
The extent of sex differences in childhood language development is unclear. We conducted a systematic literature review synthesizing results from studies examining sex differences in brain structure and function relevant to language development during childhood. We searched PubMed and Scopus databases, and this returned a total of 46 published studies meeting criteria for inclusion that directly examined sex differences in brain development relevant to language function in children. The results indicate that: (a) sex differences in brain structure or function do not necessarily lead to differences in language task performance; (b) evidence for sex differences in brain and language development are limited; (c) when present, sex differences often interact with a variety of factors such as age and task. Overall, the magnitude of sexual dimorphism of brain developmental trajectories associated with language is not as significant as previously thought. Sex differences were found, however, in studies employing tighter age ranges. This suggests that sex differences may be more prominent during certain developmental stages but are negligible in other stages, likely due to different rates of maturation between the sexes. More research is needed to improve our understanding of how sex differences may arise due to the influence of sex hormones and developmental stages, and how these differences may lead to differences in various language task performance. These studies are expected to provide normative information that may be used in studies examining neurodevelopmental disorders that frequently affect more males than females, and also often affect language development.