title: Specific polar subpopulations of astral microtubules control spindle orientation and symmetric neural stem cell division.
abstract: Mitotic spindle orientation is crucial for symmetric vs asymmetric cell division and depends on astral microtubules. Here, we show that distinct subpopulations of astral microtubules exist, which have differential functions in regulating spindle orientation and division symmetry. Specifically, in polarized stem cells of developing mouse neocortex, astral microtubules reaching the apical and basal cell cortex, but not those reaching the central cell cortex, are more abundant in symmetrically than asymmetrically dividing cells and reduce spindle orientation variability. This promotes symmetric divisions by maintaining an apico-basal cleavage plane. The greater abundance of apical/basal astrals depends on a higher concentration, at the basal cell cortex, of LGN, a known spindle-cell cortex linker. Furthermore, newly developed specific microtubule perturbations that selectively decrease apical/basal astrals recapitulate the symmetric-to-asymmetric division switch and suffice to increase neurogenesis in vivo. Thus, our study identifies a novel link between cell polarity, astral microtubules, and spindle orientation in morphogenesis.
authors.affiliation: Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany.
authors.forename: Felipe
authors.initials: F
authors.lastname: Mora-Bermúdez
authors.affiliation: RIKEN Center for Developmental Biology, Kobe, Japan.
authors.forename: Fumio
authors.initials: F
authors.lastname: Matsuzaki
authors.affiliation: Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany.
authors.forename: Wieland B
authors.initials: WB
authors.lastname: Huttner
mesh_terms: D000818:Animals; D001921:Brain / Q000502:physiology; D002453:Cell Cycle; D002455:Cell Division; D016764:Cell Polarity; D049109:Cell Proliferation; D002540:Cerebral Cortex / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D008870:Microtubules / Q000502:physiology*; D058953:Neural Stem Cells / Q000166:cytology*; D015739:Nocodazole / Q000737:chemistry; D017434:Protein Structure, Tertiary; D008941:Spindle Apparatus; D013234:Stem Cells / Q000166:cytology; D014741:Video Recording
chemical_list: D015739:Nocodazole
keywords: astral microtubules; asymmetric cell division; cell biology; developmental biology; mouse; neural stem cells; neurogenesis; nocodazole; spindle orientation; stem cells