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Your search keyword '"Gabrielle M. Sejourne"' showing total 2 results
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2 results on '"Gabrielle M. Sejourne"'

1. Rewiring of human neurodevelopmental gene regulatory programs by human accelerated regions

Author

Connor J. Kenny, Ellen M DeGennaro, Andrew B. Stergachis, Lariza M. Rento, Marc Beaudin, M. Aurel Nagy, Peter P. Wang, Kelly M. Girskis, Taehwan Shin, Michael E. Greenberg, Elizabeth A. Pollina, Peter V. Kharchenko, Ryan N. Doan, Julia L. Scotellaro, Xuyu Qian, Nenad Sestan, Jean Fan, Brian M. Debo, Janet H.T. Song, Dilenny M. Gonzalez, André M. M. Sousa, Rebecca C. Yeh, Christopher A. Walsh, Matthew B. Johnson, and Gabrielle M. Sejourne

Subjects
Epigenomics, Cell type, Pan troglodytes, General Neuroscience, Ferrets, Brain, Gene Expression Regulation, Developmental, Biology, Cell cycle, Human accelerated regions, Biological Evolution, Evolution, Molecular, Mice, HARS, Animals, Humans, Macaca, Human genome, Gene Regulatory Networks, Epigenetics, Enhancer, Gene, Neuroscience
Abstract

Summary Human accelerated regions (HARs) are the fastest-evolving regions of the human genome, and many are hypothesized to function as regulatory elements that drive human-specific gene regulatory programs. We interrogate the in vitro enhancer activity and in vivo epigenetic landscape of more than 3,100 HARs during human neurodevelopment, demonstrating that many HARs appear to act as neurodevelopmental enhancers and that sequence divergence at HARs has largely augmented their neuronal enhancer activity. Furthermore, we demonstrate PPP1R17 to be a putative HAR-regulated gene that has undergone remarkable rewiring of its cell type and developmental expression patterns between non-primates and primates and between non-human primates and humans. Finally, we show that PPP1R17 slows neural progenitor cell cycle progression, paralleling the cell cycle length increase seen predominantly in primate and especially human neurodevelopment. Our findings establish HARs as key components in rewiring human-specific neurodevelopmental gene regulatory programs and provide an integrated resource to study enhancer activity of specific HARs.

Published
2020

2. Posterior neocortex-specific regulation of neuronal migration by CEP85L identifies maternal centriole-dependent activation of CDK5

Author

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

Subjects
Male, 0301 basic medicine, Oncogene Proteins, Fusion, Centriole, Cell, Lissencephaly, Neocortex, Nerve Tissue Proteins, Microtubules, Article, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Cell Movement, medicine, Humans, pachygyria, genetics, Child, Centrioles, Neurons, biology, neurodevelopment, General Neuroscience, Cyclin-dependent kinase 5, Cyclin-Dependent Kinase 5, Microtubule cytoskeleton organization, medicine.disease, Cell biology, Cytoskeletal Proteins, 030104 developmental biology, Tubulin, medicine.anatomical_structure, centrosome, LCDK5, nervous system, Centrosome, Child, Preschool, biology.protein, Female, De novo, CEP85, 030217 neurology & neurosurgery, lissencephaly
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. Refereed/Peer-reviewed

Published
2020

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