title: Differential Mitochondrial Requirements for Radially and Non-radially Migrating Cortical Neurons: Implications for Mitochondrial Disorders.
abstract: 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.
authors.affiliation: School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Developmental, Regenerative and Stem Cell Biology, Biomedical Graduate Group, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Erika G
authors.initials: EG
authors.lastname: Lin-Hendel
authors.affiliation: Center for Mitochondrial and Epigenomic Medicine, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA; Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Meagan J
authors.initials: MJ
authors.lastname: McManus
authors.affiliation: Center for Mitochondrial and Epigenomic Medicine, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA; Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Douglas C
authors.initials: DC
authors.lastname: Wallace
authors.affiliation: Department of Psychiatry, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA. Electronic address: sande@mail.med.upenn.edu.
authors.forename: Stewart A
authors.initials: SA
authors.lastname: Anderson
authors.affiliation: Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA. Electronic address: jagolden@partners.org.
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Golden
mesh_terms: D033741:Adenine Nucleotide Translocator 1 / Q000172:deficiency / Q000378:metabolism; D000818:Animals; D002465:Cell Movement; D018385:Centrosome / Q000378:metabolism; D002540:Cerebral Cortex / Q000473:pathology*; D004622:Embryo, Mammalian / Q000473:pathology; D005260:Female; D007395:Interneurons / Q000473:pathology; D008297:Male; D008810:Mice, Inbred C57BL; D008928:Mitochondria / Q000378:metabolism*; D028361:Mitochondrial Diseases / Q000473:pathology*; D009154:Mutation / Q000235:genetics; D009474:Neurons / Q000378:metabolism*; D010085:Oxidative Phosphorylation
chemical_list: D033741:Adenine Nucleotide Translocator 1