Sodium Channel SCN3A (Na(V)1.3) Regulation of Human Cerebral Cortical Folding and Oral Motor Development
| Autor: | Taehwan Shin, Connor J. Kenny, Grazia M.S. Mancini, Carsten G. Bönnemann, R. Sean Hill, Christopher A. Walsh, Eva Andermann, Martina Wilke, Anna-Kaisa Anttonen, Ryan N. Doan, Ritva Paetau, Kiho Im, Anna-Elina Lehesjoki, Marie Claire Y. de Wit, Ahram Jang, László Sztriha, Rebeca Borges-Monroy, A. James Barkovich, Oili Salonen, Dina Amrom, Maria K. Lehtinen, Annapurna Poduri, Livija Medne, Jaakko Ignatius, Jennifer N. Partlow, Jonathan L. Hecht, Allen Y. Chen, Richard S. Smith, Vijay S. Ganesh |
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| Přispěvatelé: | Clinical Genetics, Neurology, Anna-Elina Lehesjoki / Principal Investigator, Department of Medical and Clinical Genetics, Neuroscience Center, Medicum, Research Programme for Molecular Neurology, Research Programs Unit, University of Helsinki, Clinicum, Department of Diagnostics and Therapeutics, HUS Medical Imaging Center, Children's Hospital, Lastenneurologian yksikkö |
| Rok vydání: | 2018 |
| Předmět: |
Male
0301 basic medicine PERISYLVIAN POLYMICROGYRIA Neurodegenerative Ion Channels Sodium Channels 3124 Neurology and psychiatry SCN3A Cell Movement Cortex (anatomy) NAV1.3 Voltage-Gated Sodium Channel Polymicrogyria 2.1 Biological and endogenous factors Psychology SCN1A Aetiology Child NEURONS EPILEPSY Pediatric Cerebral Cortex Cultured General Neuroscience Outer Radial Glia Cortical Development Middle Aged Na(V)1.3 Pedigree Na(V)1.1 medicine.anatomical_structure Neurological Female Cognitive Sciences ALPHA-SUBUNIT RADIAL GLIA Adult EXPRESSION REVERSE NA+/CA2+ EXCHANGE Adolescent Cells 1.1 Normal biological development and functioning Subventricular zone Biology Language Development Article CONTRIBUTES 03 medical and health sciences Channelopathy Underpinning research medicine Animals Speech Humans Preschool Oromotor Epilepsy Neurology & Neurosurgery Sodium channel Sodium Ferrets Neurosciences 3112 Neurosciences Infant Voltage-Gated Sodium Channel IN-VITRO Perinatal Period - Conditions Originating in Perinatal Period Stem Cell Research medicine.disease Perisylvian polymicrogyria Megalencephaly ta3124 Brain Disorders NEURAL PROGENITORS HEK293 Cells 030104 developmental biology NAV1 Neuroscience |
| Zdroj: | Neuron, 99(5), 905-+. Cell Press Neuron, vol 99, iss 5 |
| ISSN: | 0896-6273 |
| Popis: | Channelopathies are disorders caused by abnormal ion channel function in differentiated excitable tissues. We discovered a unique neurodevelopmental channelopathy resulting from pathogenic variants in SCN3A, a gene encoding the voltage-gated sodium channel Na(V)1.3. Pathogenic Na(V)1.3 channels showed altered biophysical properties including increased persistent current. Remarkably, affected individuals showed disrupted folding (polymicrogyria) of the perisylvian cortex of the brain but did not typically exhibit epilepsy; they presented with prominent speech and oral motor dysfunction, implicating SCN3A in prenatal development of human cortical language areas. The development of this disorder parallels SCN3A expression, which we observed to be highest early in fetal cortical development in progenitor cells of the outer subventricular zone and cortical plate neurons and decreased postnatally, when SCN1A (Na(V)1.1) expression increased. Disrupted cerebral cortical folding and neuronal migration were recapitulated in ferrets expressing the mutant channel, underscoring the unexpected role of SCN3A in progenitor cells and migrating neurons. |
| Databáze: | OpenAIRE |
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