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Publication : MALS-3 regulates polarity and early neurogenesis in the developing cerebral cortex.

First Author  Srinivasan K Year  2008
Journal  Development Volume  135
Issue  10 Pages  1781-90
PubMed ID  18403412 Mgi Jnum  J:134686
Mgi Id  MGI:3789530 Doi  10.1242/dev.013847
Citation  Srinivasan K, et al. (2008) MALS-3 regulates polarity and early neurogenesis in the developing cerebral cortex. Development 135(10):1781-90
abstractText  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.
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