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ASPP2 binds Par-3 and controls the polarity and proliferation of neural progenitors during CNS development

ASPP2 binds Par-3 and controls the polarity and proliferation of neural progenitors during CNS development
ASPP2 binds Par-3 and controls the polarity and proliferation of neural progenitors during CNS development
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? 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.
1534-5807
126-137
Sottocornola, Roberta
0e81dee8-b7de-4095-a551-bbdbab2426e0
Royer, Christophe
6f928270-64ef-42ba-9a6b-ebb4d8403a3a
Vives, Virginie
6c89fef5-dc42-4992-a744-2493781e841e
Tordella, Luca
3acb6647-f205-467c-8a2b-22592a115476
Zhong, Shan
6d0d5d48-c69b-444d-acae-fd7a3fd76e23
Wang, Yihua
f5044a95-60a7-42d2-87d6-5f1f789e3a7e
Ratnayaka, Indrika
73e69863-2f4f-4c01-851c-c91d855b0760
Shipman, Mark
71e42d74-87e1-4cfc-81fb-55758894596b
Cheung, Amanda
56f63ad5-e84a-469a-91c0-1b983d4ce915
Gaston-Massuet, Carles
41dccf57-338c-4d8d-b8a4-868e1966bd23
Ferretti, Patrizia
21e02d90-ce96-4580-a979-302342ae0f63
Molnár, Zoltán
9b15b8da-6939-43c6-946f-6c7f213baaf7
Lu, Xin
a681bac0-d6d1-4e8e-a642-4ce42ae2cc9d
Sottocornola, Roberta
0e81dee8-b7de-4095-a551-bbdbab2426e0
Royer, Christophe
6f928270-64ef-42ba-9a6b-ebb4d8403a3a
Vives, Virginie
6c89fef5-dc42-4992-a744-2493781e841e
Tordella, Luca
3acb6647-f205-467c-8a2b-22592a115476
Zhong, Shan
6d0d5d48-c69b-444d-acae-fd7a3fd76e23
Wang, Yihua
f5044a95-60a7-42d2-87d6-5f1f789e3a7e
Ratnayaka, Indrika
73e69863-2f4f-4c01-851c-c91d855b0760
Shipman, Mark
71e42d74-87e1-4cfc-81fb-55758894596b
Cheung, Amanda
56f63ad5-e84a-469a-91c0-1b983d4ce915
Gaston-Massuet, Carles
41dccf57-338c-4d8d-b8a4-868e1966bd23
Ferretti, Patrizia
21e02d90-ce96-4580-a979-302342ae0f63
Molnár, Zoltán
9b15b8da-6939-43c6-946f-6c7f213baaf7
Lu, Xin
a681bac0-d6d1-4e8e-a642-4ce42ae2cc9d

Sottocornola, Roberta, Royer, Christophe, Vives, Virginie, Tordella, Luca, Zhong, Shan, Wang, Yihua, Ratnayaka, Indrika, Shipman, Mark, Cheung, Amanda, Gaston-Massuet, Carles, Ferretti, Patrizia, Molnár, Zoltán and Lu, Xin (2010) ASPP2 binds Par-3 and controls the polarity and proliferation of neural progenitors during CNS development. Developmental Cell, 19 (1), 126-137. (doi:10.1016/j.devcel.2010.06.003).

Record type: Article

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? 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.

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Accepted/In Press date: 10 May 2010
e-pub ahead of print date: 8 July 2010
Published date: 10 July 2010
Organisations: Centre for Biological Sciences

Identifiers

Local EPrints ID: 385906
URI: http://eprints.soton.ac.uk/id/eprint/385906
ISSN: 1534-5807
PURE UUID: b7041adc-fb62-48b6-a400-e9ea91c1f320
ORCID for Yihua Wang: ORCID iD orcid.org/0000-0001-5561-0648

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Date deposited: 26 Jan 2016 09:57
Last modified: 17 Dec 2019 01:33

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Contributors

Author: Roberta Sottocornola
Author: Christophe Royer
Author: Virginie Vives
Author: Luca Tordella
Author: Shan Zhong
Author: Yihua Wang ORCID iD
Author: Indrika Ratnayaka
Author: Mark Shipman
Author: Amanda Cheung
Author: Carles Gaston-Massuet
Author: Patrizia Ferretti
Author: Zoltán Molnár
Author: Xin Lu

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