Memo1-Mediated Tiling of Radial Glial Cells Facilitates Cerebral Cortical Development

• Published in: Neuron (Cambridge, Mass.) Vol. 103; no. 5; pp. 836 - 852.e5
• Main Authors: Nakagawa, Naoki, Plestant, Charlotte, Yabuno-Nakagawa, Keiko, Li, Jingjun, Lee, Janice, Huang, Chu-Wei, Lee, Amelia, Krupa, Oleh, Adhikari, Aditi, Thompson, Suriya, Rhynes, Tamille, Arevalo, Victoria, Stein, Jason L., Molnár, Zoltán, Badache, Ali, Anton, E.S.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 04.09.2019; Elsevier Limited; Elsevier
• Subjects: Animals; Autism; Autistic Disorder; Autistic Disorder - genetics; Cell Movement; Cell Movement - genetics; Cell Polarity; Cellular Biology; Cerebellum; Cerebellum - embryology; Cerebral Cortex; Cerebral Cortex - cytology; Cerebral Cortex - embryology; Cerebral Cortex - metabolism; Clonal deletion; Cloning; corticogenesis; Ependymoglial Cells; Ependymoglial Cells - cytology; Ependymoglial Cells - metabolism; Experiments; Gene Knockdown Techniques; Glial cells; HEK293 Cells; Hippocampus; Hippocampus - embryology; Humans; Intracellular Signaling Peptides and Proteins; Intracellular Signaling Peptides and Proteins - genetics; Life Sciences; MADM; Memo1; Mice; microtubule minus end; Microtubule-Associated Proteins; Microtubule-Associated Proteins - metabolism; Microtubules; Microtubules - metabolism; Morphology; Neocortex; Neocortex - cytology; Neocortex - embryology; Neocortex - metabolism; Neural Stem Cells; Neural Stem Cells - cytology; Neural Stem Cells - metabolism; Neurogenesis; Neurons; Neurons - cytology; Neurons - metabolism; progenitors; Protein Transport; Proteins; radial glia; Radial glial cells; Receptors, G-Protein-Coupled; Receptors, G-Protein-Coupled - metabolism; Retinal ganglion cells; progenitors; corticogenesis; microtubule minus end; radial glia; Memo1; MADM; autism
• ISSN: 0896-6273; 1097-4199
• DOI: 10.1016/j.neuron.2019.05.049

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. [Display omitted] •Radial glial tiling regulates neuronal organization during cortical formation•Memo1 is a determinant of radial glial cell (RGC) tiling•Memo1 modulates microtubule stability and minus-end protein, CAMSAP2, function•Disrupted radial glial tiling may contribute to cortical malformations in ASD Tiled radial glial cells (RGCs) provide an instructive template for the formation of the cerebral cortex. Memo1 regulates RGC tiling underlying radial unit formation and neuronal laminar organization. Mutations in MEMO1 and resultant cortical malformations may contribute to autism risk.