title: MALS-3 regulates polarity and early neurogenesis in the developing cerebral cortex.
abstract: Apicobasal polarity plays an important role in regulating asymmetric cell divisions by neural progenitor cells (NPCs) in invertebrates, but the role of polarity in mammalian NPCs is poorly understood. Here, we characterize the function of the PDZ domain protein MALS-3 in the developing cerebral cortex. We find that MALS-3 is localized to the apical domain of NPCs. Mice lacking all three MALS genes fail to localize the polarity proteins PATJ and PALS1 apically in NPCs, whereas the formation and maintenance of adherens junctions appears normal. In the absence of MALS proteins, early NPCs progressed more slowly through the cell cycle, and their daughter cells were more likely to exit the cell cycle and differentiate into neurons. Interestingly, these effects were transient; NPCs recovered normal cell cycle properties during late neurogenesis. Experiments in which MALS-3 was targeted to the entire membrane resulted in a breakdown of apicobasal polarity, loss of adherens junctions, and a slowing of the cell cycle. Our results suggest that MALS-3 plays a role in maintaining apicobasal polarity and is required for normal neurogenesis in the developing cortex.
authors.affiliation: Department of Biological Sciences, Stanford University, Stanford, CA 94305, USA.
authors.forename: Karpagam
authors.initials: K
authors.lastname: Srinivasan
authors.forename: Jason
authors.initials: J
authors.lastname: Roosa
authors.forename: Olav
authors.initials: O
authors.lastname: Olsen
authors.forename: Soung-Hun
authors.initials: SH
authors.lastname: Lee
authors.forename: David S
authors.initials: DS
authors.lastname: Bredt
authors.forename: Susan K
authors.initials: SK
authors.lastname: McConnell
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000502:physiology*; D022005:Adherens Junctions / Q000378:metabolism; D000818:Animals; D002453:Cell Cycle / Q000502:physiology; D002454:Cell Differentiation; D002462:Cell Membrane / Q000378:metabolism; D016764:Cell Polarity / Q000502:physiology*; D002540:Cerebral Cortex / Q000166:cytology / Q000196:embryology* / Q000378:metabolism; D005260:Female; D008565:Membrane Proteins / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D019579:Neocortex / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000502:physiology*; D051381:Rats; D013234:Stem Cells / Q000166:cytology / Q000502:physiology
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C114672:Lin7c protein, mouse; C119526:Lin7c protein, rat; D008565:Membrane Proteins