Differential Mitochondrial Requirements for Radially and Non-radially Migrating Cortical Neurons: Implications for Mitochondrial Disorders
Mitochondrial dysfunction has been increasingly linked to neurodevelopmental disorders such as intellectual disability, childhood epilepsy, and autism spectrum disorder, conditions also associated with cortical GABAergic interneuron dysfunction. Although interneurons have some of the highest metabol...
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doaj-a39b85ad2b7e4b618e60729dac293b2d2020-11-24T22:01:24ZengElsevierCell Reports2211-12472016-04-0115222923710.1016/j.celrep.2016.03.024Differential Mitochondrial Requirements for Radially and Non-radially Migrating Cortical Neurons: Implications for Mitochondrial DisordersErika G. Lin-Hendel0Meagan J. McManus1Douglas C. Wallace2Stewart A. Anderson3Jeffrey A. Golden4School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104, USACenter for Mitochondrial and Epigenomic Medicine, Children’s Hospital of Philadelphia, Philadelphia, PA 19104, USACenter for Mitochondrial and Epigenomic Medicine, Children’s Hospital of Philadelphia, Philadelphia, PA 19104, USADepartment of Psychiatry, Children’s Hospital of Philadelphia, Philadelphia, PA 19104, USADepartment of Pathology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115, USAMitochondrial dysfunction has been increasingly linked to neurodevelopmental disorders such as intellectual disability, childhood epilepsy, and autism spectrum disorder, conditions also associated with cortical GABAergic interneuron dysfunction. Although interneurons have some of the highest metabolic demands in the postnatal brain, the importance of mitochondria during interneuron development is unknown. We find that interneuron migration from the basal forebrain to the neocortex is highly sensitive to perturbations in oxidative phosphorylation. Both pharmacologic and genetic inhibition of adenine nucleotide transferase 1 (Ant1) disrupts the non-radial migration of interneurons, but not the radial migration of cortical projection neurons. The selective dependence of cortical interneuron migration on oxidative phosphorylation may be a mechanistic pathway upon which multiple developmental and metabolic pathologies converge.http://www.sciencedirect.com/science/article/pii/S2211124716302807 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Erika G. Lin-Hendel Meagan J. McManus Douglas C. Wallace Stewart A. Anderson Jeffrey A. Golden |
spellingShingle |
Erika G. Lin-Hendel Meagan J. McManus Douglas C. Wallace Stewart A. Anderson Jeffrey A. Golden Differential Mitochondrial Requirements for Radially and Non-radially Migrating Cortical Neurons: Implications for Mitochondrial Disorders Cell Reports |
author_facet |
Erika G. Lin-Hendel Meagan J. McManus Douglas C. Wallace Stewart A. Anderson Jeffrey A. Golden |
author_sort |
Erika G. Lin-Hendel |
title |
Differential Mitochondrial Requirements for Radially and Non-radially Migrating Cortical Neurons: Implications for Mitochondrial Disorders |
title_short |
Differential Mitochondrial Requirements for Radially and Non-radially Migrating Cortical Neurons: Implications for Mitochondrial Disorders |
title_full |
Differential Mitochondrial Requirements for Radially and Non-radially Migrating Cortical Neurons: Implications for Mitochondrial Disorders |
title_fullStr |
Differential Mitochondrial Requirements for Radially and Non-radially Migrating Cortical Neurons: Implications for Mitochondrial Disorders |
title_full_unstemmed |
Differential Mitochondrial Requirements for Radially and Non-radially Migrating Cortical Neurons: Implications for Mitochondrial Disorders |
title_sort |
differential mitochondrial requirements for radially and non-radially migrating cortical neurons: implications for mitochondrial disorders |
publisher |
Elsevier |
series |
Cell Reports |
issn |
2211-1247 |
publishDate |
2016-04-01 |
description |
Mitochondrial dysfunction has been increasingly linked to neurodevelopmental disorders such as intellectual disability, childhood epilepsy, and autism spectrum disorder, conditions also associated with cortical GABAergic interneuron dysfunction. Although interneurons have some of the highest metabolic demands in the postnatal brain, the importance of mitochondria during interneuron development is unknown. We find that interneuron migration from the basal forebrain to the neocortex is highly sensitive to perturbations in oxidative phosphorylation. Both pharmacologic and genetic inhibition of adenine nucleotide transferase 1 (Ant1) disrupts the non-radial migration of interneurons, but not the radial migration of cortical projection neurons. The selective dependence of cortical interneuron migration on oxidative phosphorylation may be a mechanistic pathway upon which multiple developmental and metabolic pathologies converge. |
url |
http://www.sciencedirect.com/science/article/pii/S2211124716302807 |
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