ASPP2 binds Par-3 and controls the polarity and proliferation of neural progenitors during CNS development
Roberta Sottocornola1, Christophe Royer, Virginie Vives
1Ludwig Institute for Cancer Research, Nuffield Department of Clinical Medicine, University of Oxford, Old Road Campus Research Building, Headington, Oxford OX3 7DQ, UK.
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.
Insights
ASPP2 controls neural progenitor cell polarity and proliferation during central nervous system (CNS) development. This protein maintains tissue organization by regulating cell junctions and nuclear migration, impacting neuroblastic rosette formation.
Area of Science:
- Neuroscience
- Developmental Biology
- Cancer Biology
Background:
- Cell polarity is crucial for central nervous system (CNS) development.
- Disrupted cell polarity is implicated in various cancers.
- ASPP2 functions as a tumor suppressor and activates the p53 family.
Purpose of the Study:
- To investigate the role of ASPP2 in neural progenitor cell polarity and proliferation in vivo.
- To elucidate the molecular mechanisms by which ASPP2 controls CNS development.
- To understand the link between ASPP2, cell polarity, and tumor formation.
Main Methods:
- In vivo studies of neural progenitor cells.
- Analysis of cell polarity markers and cell junctions.
- Investigation of protein-protein interactions (ASPP2 and Par-3).
- Assessment of interkinetic nuclear migration and tissue lamination.
Main Results:
- ASPP2 regulates neural progenitor polarity and proliferation, forming structures resembling primitive neuroepithelial tumors.
- ASPP2 influences interkinetic nuclear migration and CNS tissue lamination.
- ASPP2 maintains tight and adherens junction integrity by binding and controlling the localization of Par-3.
Conclusions:
- ASPP2 is a key regulator of cell polarity and tissue organization in the developing CNS.
- ASPP2's interaction with Par-3 is essential for controlling cell proliferation and maintaining junctional integrity.
- Dysregulation of ASPP2 may contribute to tumor formation by disrupting normal developmental processes.
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