Posterior Neocortex-Specific Regulation of Neuronal Migration by CEP85L Identifies Maternal Centriole-Dependent Activation of CDK5

Andrew Kodani; Connor Kenny; Abbe Lai; Dilenny M. Gonzalez; Edward Stronge; Gabrielle M. Sejourne; Laura Isacco; Jennifer N. Partlow; Anne O'Donnell; Kirsty McWalter; Alicia B. Byrne; A. James Barkovich; Edward Yang; R. Sean Hill; Pawel Gawlinski; Wojciech Wiszniewski; Julie S. Cohen; S. Ali Fatemi; Kristin W. Baranano; Mustafa Sahin; David G. Vossler; Christopher J. Yuskaitis; Christopher A. Walsh

doi:10.1016/j.neuron.2020.01.030

Posterior Neocortex-Specific Regulation of Neuronal Migration by CEP85L Identifies Maternal Centriole-Dependent Activation of CDK5

Andrew Kodani, Connor Kenny, Abbe Lai, Dilenny M. Gonzalez, Edward Stronge, Gabrielle M. Sejourne, Laura Isacco, Jennifer N. Partlow, Anne O'Donnell, Kirsty McWalter, Alicia B. Byrne, A. James Barkovich, Edward Yang, R. Sean Hill, Pawel Gawlinski, Wojciech Wiszniewski, Julie S. Cohen, S. Ali Fatemi, Kristin W. Baranano, Mustafa SahinDavid G. Vossler, Christopher J. Yuskaitis, Christopher A. Walsh

Research output: Contribution to journal › Article › peer-review

4 Scopus citations

Abstract

Genes mutated in human neuronal migration disorders encode tubulin proteins and a variety of tubulin-binding and -regulating proteins, but it is very poorly understood how these proteins function together to coordinate migration. Additionally, the way in which regional differences in neocortical migration are controlled is completely unknown. Here we describe a new syndrome with remarkably region-specific effects on neuronal migration in the posterior cortex, reflecting de novo variants in CEP85L. We show that CEP85L is required cell autonomously in vivo and in vitro for migration, that it localizes to the maternal centriole, and that it forms a complex with many other proteins required for migration, including CDK5, LIS1, NDE1, KIF2A, and DYNC1H1. Loss of CEP85L disrupts CDK5 localization and activation, leading to centrosome disorganization and disrupted microtubule cytoskeleton organization. Together, our findings suggest that CEP85L highlights a complex that controls CDK5 activity to promote neuronal migration.

Original language	English (US)
Pages (from-to)	246-255.e6
Journal	Neuron
Volume	106
Issue number	2
DOIs	https://doi.org/10.1016/j.neuron.2020.01.030
State	Published - Apr 22 2020

Keywords

CDK5
CEP85L
Centrosome
De novo
Lissencephaly
Pachygyria
genetics
neurodevelopment

ASJC Scopus subject areas

General Neuroscience

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10.1016/j.neuron.2020.01.030

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Kodani, A., Kenny, C., Lai, A., Gonzalez, D. M., Stronge, E., Sejourne, G. M., Isacco, L., Partlow, J. N., O'Donnell, A., McWalter, K., Byrne, A. B., Barkovich, A. J., Yang, E., Hill, R. S., Gawlinski, P., Wiszniewski, W., Cohen, J. S., Fatemi, S. A., Baranano, K. W., ... Walsh, C. A. (2020). Posterior Neocortex-Specific Regulation of Neuronal Migration by CEP85L Identifies Maternal Centriole-Dependent Activation of CDK5. Neuron, 106(2), 246-255.e6. https://doi.org/10.1016/j.neuron.2020.01.030

Kodani, A, Kenny, C, Lai, A, Gonzalez, DM, Stronge, E, Sejourne, GM, Isacco, L, Partlow, JN, O'Donnell, A, McWalter, K, Byrne, AB, Barkovich, AJ, Yang, E, Hill, RS, Gawlinski, P, Wiszniewski, W, Cohen, JS, Fatemi, SA, Baranano, KW, Sahin, M, Vossler, DG, Yuskaitis, CJ & Walsh, CA 2020, 'Posterior Neocortex-Specific Regulation of Neuronal Migration by CEP85L Identifies Maternal Centriole-Dependent Activation of CDK5', Neuron, vol. 106, no. 2, pp. 246-255.e6. https://doi.org/10.1016/j.neuron.2020.01.030

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title = "Posterior Neocortex-Specific Regulation of Neuronal Migration by CEP85L Identifies Maternal Centriole-Dependent Activation of CDK5",

abstract = "Genes mutated in human neuronal migration disorders encode tubulin proteins and a variety of tubulin-binding and -regulating proteins, but it is very poorly understood how these proteins function together to coordinate migration. Additionally, the way in which regional differences in neocortical migration are controlled is completely unknown. Here we describe a new syndrome with remarkably region-specific effects on neuronal migration in the posterior cortex, reflecting de novo variants in CEP85L. We show that CEP85L is required cell autonomously in vivo and in vitro for migration, that it localizes to the maternal centriole, and that it forms a complex with many other proteins required for migration, including CDK5, LIS1, NDE1, KIF2A, and DYNC1H1. Loss of CEP85L disrupts CDK5 localization and activation, leading to centrosome disorganization and disrupted microtubule cytoskeleton organization. Together, our findings suggest that CEP85L highlights a complex that controls CDK5 activity to promote neuronal migration.",

keywords = "CDK5, CEP85L, Centrosome, De novo, Lissencephaly, Pachygyria, genetics, neurodevelopment",

author = "Andrew Kodani and Connor Kenny and Abbe Lai and Gonzalez, {Dilenny M.} and Edward Stronge and Sejourne, {Gabrielle M.} and Laura Isacco and Partlow, {Jennifer N.} and Anne O'Donnell and Kirsty McWalter and Byrne, {Alicia B.} and Barkovich, {A. James} and Edward Yang and Hill, {R. Sean} and Pawel Gawlinski and Wojciech Wiszniewski and Cohen, {Julie S.} and Fatemi, {S. Ali} and Baranano, {Kristin W.} and Mustafa Sahin and Vossler, {David G.} and Yuskaitis, {Christopher J.} and Walsh, {Christopher A.}",

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year = "2020",

month = apr,

day = "22",

doi = "10.1016/j.neuron.2020.01.030",

language = "English (US)",

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AU - Kodani, Andrew

AU - Kenny, Connor

AU - Lai, Abbe

AU - Gonzalez, Dilenny M.

AU - Stronge, Edward

AU - Sejourne, Gabrielle M.

AU - Isacco, Laura

AU - Partlow, Jennifer N.

AU - O'Donnell, Anne

AU - McWalter, Kirsty

AU - Byrne, Alicia B.

AU - Barkovich, A. James

AU - Yang, Edward

AU - Hill, R. Sean

AU - Gawlinski, Pawel

AU - Wiszniewski, Wojciech

AU - Cohen, Julie S.

AU - Fatemi, S. Ali

AU - Baranano, Kristin W.

AU - Sahin, Mustafa

AU - Vossler, David G.

AU - Yuskaitis, Christopher J.

AU - Walsh, Christopher A.

PY - 2020/4/22

Y1 - 2020/4/22

N2 - Genes mutated in human neuronal migration disorders encode tubulin proteins and a variety of tubulin-binding and -regulating proteins, but it is very poorly understood how these proteins function together to coordinate migration. Additionally, the way in which regional differences in neocortical migration are controlled is completely unknown. Here we describe a new syndrome with remarkably region-specific effects on neuronal migration in the posterior cortex, reflecting de novo variants in CEP85L. We show that CEP85L is required cell autonomously in vivo and in vitro for migration, that it localizes to the maternal centriole, and that it forms a complex with many other proteins required for migration, including CDK5, LIS1, NDE1, KIF2A, and DYNC1H1. Loss of CEP85L disrupts CDK5 localization and activation, leading to centrosome disorganization and disrupted microtubule cytoskeleton organization. Together, our findings suggest that CEP85L highlights a complex that controls CDK5 activity to promote neuronal migration.

AB - Genes mutated in human neuronal migration disorders encode tubulin proteins and a variety of tubulin-binding and -regulating proteins, but it is very poorly understood how these proteins function together to coordinate migration. Additionally, the way in which regional differences in neocortical migration are controlled is completely unknown. Here we describe a new syndrome with remarkably region-specific effects on neuronal migration in the posterior cortex, reflecting de novo variants in CEP85L. We show that CEP85L is required cell autonomously in vivo and in vitro for migration, that it localizes to the maternal centriole, and that it forms a complex with many other proteins required for migration, including CDK5, LIS1, NDE1, KIF2A, and DYNC1H1. Loss of CEP85L disrupts CDK5 localization and activation, leading to centrosome disorganization and disrupted microtubule cytoskeleton organization. Together, our findings suggest that CEP85L highlights a complex that controls CDK5 activity to promote neuronal migration.

KW - CDK5

KW - CEP85L

KW - Centrosome

KW - De novo

KW - Lissencephaly

KW - Pachygyria

KW - genetics

KW - neurodevelopment

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AN - SCOPUS:85083306241

SN - 0896-6273

VL - 106

SP - 246-255.e6

JO - Neuron

JF - Neuron

IS - 2

ER -

Posterior Neocortex-Specific Regulation of Neuronal Migration by CEP85L Identifies Maternal Centriole-Dependent Activation of CDK5

Abstract

Keywords

ASJC Scopus subject areas

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