1. ASPP2 binds Par-3 and controls the polarity and proliferation of neural progenitors during CNS development.
- Author
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Sottocornola R, Royer C, Vives V, Tordella L, Zhong S, Wang Y, Ratnayaka I, Shipman M, Cheung A, Gaston-Massuet C, Ferretti P, Molnár Z, and Lu X
- Subjects
- Adaptor Proteins, Signal Transducing, Animals, Base Sequence, Cell Cycle Proteins, Cell Polarity physiology, Cell Proliferation, Central Nervous System abnormalities, Central Nervous System cytology, Central Nervous System metabolism, DNA Primers genetics, Female, Mice, Mice, Inbred BALB C, Mice, Inbred C57BL, Mice, Knockout, Neocortex abnormalities, Neocortex embryology, Neurons cytology, Neurons metabolism, Pregnancy, Protein Binding, Retina abnormalities, Retina embryology, Tight Junctions metabolism, Tight Junctions ultrastructure, Tumor Suppressor Proteins deficiency, Tumor Suppressor Proteins genetics, Cell Adhesion Molecules physiology, Central Nervous System embryology, Tumor Suppressor Proteins physiology
- Abstract
Cell polarity plays a key role in the development of the central nervous system (CNS). Interestingly, disruption of cell polarity is seen in many cancers. ASPP2 is a haplo-insufficient tumor suppressor and an activator of the p53 family. In this study, we show that ASPP2 controls the polarity and proliferation of neural progenitors in vivo, leading to the formation of neuroblastic rosettes that resemble primitive neuroepithelial tumors. Consistent with its role in cell polarity, ASPP2 influences interkinetic nuclear migration and lamination during CNS development. Mechanistically, ASPP2 maintains the integrity of tight/adherens junctions. ASPP2 binds Par-3 and controls its apical/junctional localization without affecting its expression or Par-3/aPKC lambda binding. The junctional localization of ASPP2 and Par-3 is interdependent, suggesting that they are prime targets for each other. These results identify ASPP2 as a regulator of Par-3, which plays a key role in controlling cell proliferation, polarity, and tissue organization during CNS development., ((c) 2010 Elsevier Inc. All rights reserved.)
- Published
- 2010
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