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Posterior Neocortex-Specific Regulation of Neuronal Migration by CEP85L Identifies Maternal Centriole-Dependent Activation of CDK5.
Kodani, Andrew; Kenny, Connor; Lai, Abbe; Gonzalez, Dilenny M; Stronge, Edward; Sejourne, Gabrielle M; Isacco, Laura; Partlow, Jennifer N; O'Donnell, Anne; McWalter, Kirsty; Byrne, Alicia B; Barkovich, A James; Yang, Edward; Hill, R Sean; Gawlinski, Pawel; Wiszniewski, Wojciech; Cohen, Julie S; Fatemi, S Ali; Baranano, Kristin W; Sahin, Mustafa; Vossler, David G; Yuskaitis, Christopher J; Walsh, Christopher A.
Affiliation
  • Kodani A; Division of Genetics and Genomics and Howard Hughes Medical Institute, Boston Children's Hospital, Boston, MA, USA; Department of Pediatrics and Neurology, Harvard Medical School, Boston, MA, USA. Electronic address: andrew.kodani@childrens.harvard.edu.
  • Kenny C; Division of Genetics and Genomics and Howard Hughes Medical Institute, Boston Children's Hospital, Boston, MA, USA; Department of Pediatrics and Neurology, Harvard Medical School, Boston, MA, USA.
  • Lai A; Division of Genetics and Genomics and Howard Hughes Medical Institute, Boston Children's Hospital, Boston, MA, USA; Department of Pediatrics and Neurology, Harvard Medical School, Boston, MA, USA; Department of Neurology, Boston Children's Hospital, Boston, MA, USA.
  • Gonzalez DM; Division of Genetics and Genomics and Howard Hughes Medical Institute, Boston Children's Hospital, Boston, MA, USA; Department of Pediatrics and Neurology, Harvard Medical School, Boston, MA, USA.
  • Stronge E; Division of Genetics and Genomics and Howard Hughes Medical Institute, Boston Children's Hospital, Boston, MA, USA; Department of Pediatrics and Neurology, Harvard Medical School, Boston, MA, USA.
  • Sejourne GM; Division of Genetics and Genomics and Howard Hughes Medical Institute, Boston Children's Hospital, Boston, MA, USA; Department of Pediatrics and Neurology, Harvard Medical School, Boston, MA, USA.
  • Isacco L; Division of Genetics and Genomics and Howard Hughes Medical Institute, Boston Children's Hospital, Boston, MA, USA; Department of Pediatrics and Neurology, Harvard Medical School, Boston, MA, USA.
  • Partlow JN; Division of Genetics and Genomics and Howard Hughes Medical Institute, Boston Children's Hospital, Boston, MA, USA; Department of Pediatrics and Neurology, Harvard Medical School, Boston, MA, USA.
  • O'Donnell A; Division of Genetics and Genomics and Howard Hughes Medical Institute, Boston Children's Hospital, Boston, MA, USA; Department of Pediatrics and Neurology, Harvard Medical School, Boston, MA, USA; Center for Mendelian Genomics, The Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • McWalter K; GeneDX, Gaithersburg, MD, USA.
  • Byrne AB; Center for Mendelian Genomics, The Broad Institute of MIT and Harvard, Cambridge, MA, USA; Department of Genetics and Molecular Pathology, Centre for Cancer Biology, SA Pathology, Adelaide, SA, Australia; School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, SA, Australia
  • Barkovich AJ; Department of Radiology, University of California, San Francisco, San Francisco, CA, USA.
  • Yang E; Department of Radiology, Boston Children's Hospital, Boston, MA, USA.
  • Hill RS; Division of Genetics and Genomics and Howard Hughes Medical Institute, Boston Children's Hospital, Boston, MA, USA; Department of Pediatrics and Neurology, Harvard Medical School, Boston, MA, USA.
  • Gawlinski P; Department of Medical Genetics, Institute of Mother and Child, Warsaw, Poland.
  • Wiszniewski W; Department of Medical Genetics, Institute of Mother and Child, Warsaw, Poland; Department of Molecular and Medical Genetics, Oregon Health and Science University, Portland, OR, USA.
  • Cohen JS; Division of Neurogenetics, Kennedy Krieger Institute, Baltimore, MD, USA; Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • Fatemi SA; Division of Neurogenetics, Kennedy Krieger Institute, Baltimore, MD, USA; Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • Baranano KW; Division of Neurogenetics, Kennedy Krieger Institute, Baltimore, MD, USA; Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • Sahin M; Department of Neurology, Boston Children's Hospital, Boston, MA, USA.
  • Vossler DG; Department of Neurology, University of Washington, Seattle, WA, USA.
  • Yuskaitis CJ; Department of Neurology, Boston Children's Hospital, Boston, MA, USA; Division of Epilepsy and Neurophysiology, Department of Neurology, Boston Children's Hospital, Boston, MA, USA.
  • Walsh CA; Division of Genetics and Genomics and Howard Hughes Medical Institute, Boston Children's Hospital, Boston, MA, USA; Department of Pediatrics and Neurology, Harvard Medical School, Boston, MA, USA. Electronic address: christopher.walsh@childrens.harvard.edu.
Neuron ; 106(2): 246-255.e6, 2020 04 22.
Article in En | MEDLINE | ID: mdl-32097629
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.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Oncogene Proteins, Fusion / Cell Movement / Neocortex / Cytoskeletal Proteins / Cyclin-Dependent Kinase 5 / Lissencephaly / Neurons Type of study: Prognostic_studies Limits: Adult / Child / Child, preschool / Female / Humans / Male Language: En Journal: Neuron Journal subject: NEUROLOGIA Year: 2020 Document type: Article
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Oncogene Proteins, Fusion / Cell Movement / Neocortex / Cytoskeletal Proteins / Cyclin-Dependent Kinase 5 / Lissencephaly / Neurons Type of study: Prognostic_studies Limits: Adult / Child / Child, preschool / Female / Humans / Male Language: En Journal: Neuron Journal subject: NEUROLOGIA Year: 2020 Document type: Article