Mafb and c-Maf Have Prenatal Compensatory and Postnatal Antagonistic Roles in Cortical Interneuron Fate and Function

Emily Ling-Lin Pai; Daniel Vogt; Alexandra Clemente-Perez; Gabriel L. McKinsey; Frances S. Cho; Jia Sheng Hu; Matt Wimer; Anirban Paul; Siavash Fazel Darbandi; Ramon Pla; Tomasz J. Nowakowski; Lisa V. Goodrich; Jeanne T. Paz; John L.R. Rubenstein

Cell Reports (Jan 2019)

Mafb and c-Maf Have Prenatal Compensatory and Postnatal Antagonistic Roles in Cortical Interneuron Fate and Function

Emily Ling-Lin Pai,
Daniel Vogt,
Alexandra Clemente-Perez,
Gabriel L. McKinsey,
Frances S. Cho,
Jia Sheng Hu,
Matt Wimer,
Anirban Paul,
Siavash Fazel Darbandi,
Ramon Pla,
Tomasz J. Nowakowski,
Lisa V. Goodrich,
Jeanne T. Paz,
John L.R. Rubenstein

Affiliations

Emily Ling-Lin Pai: Nina Ireland Laboratory of Developmental Neurobiology, Department of Psychiatry, UCSF Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA 94158, USA; Neuroscience Graduate Program, University of California, San Francisco, San Francisco, CA 94158, USA
Daniel Vogt: Nina Ireland Laboratory of Developmental Neurobiology, Department of Psychiatry, UCSF Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA 94158, USA; Department of Pediatrics and Human Development, Michigan State University, Grand Rapids, MI 49503, USA
Alexandra Clemente-Perez: Neuroscience Graduate Program, University of California, San Francisco, San Francisco, CA 94158, USA; Department of Neurology, University of California, San Francisco, San Francisco, CA 94158, USA; Gladstone Institute of Neurological Disease, San Francisco, CA 94158, USA
Gabriel L. McKinsey: Nina Ireland Laboratory of Developmental Neurobiology, Department of Psychiatry, UCSF Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA 94158, USA
Frances S. Cho: Neuroscience Graduate Program, University of California, San Francisco, San Francisco, CA 94158, USA; Department of Neurology, University of California, San Francisco, San Francisco, CA 94158, USA; Gladstone Institute of Neurological Disease, San Francisco, CA 94158, USA
Jia Sheng Hu: Nina Ireland Laboratory of Developmental Neurobiology, Department of Psychiatry, UCSF Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA 94158, USA
Matt Wimer: Department of Neurology, University of California, San Francisco, San Francisco, CA 94158, USA; Gladstone Institute of Neurological Disease, San Francisco, CA 94158, USA
Anirban Paul: Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA
Siavash Fazel Darbandi: Nina Ireland Laboratory of Developmental Neurobiology, Department of Psychiatry, UCSF Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA 94158, USA
Ramon Pla: Nina Ireland Laboratory of Developmental Neurobiology, Department of Psychiatry, UCSF Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA 94158, USA
Tomasz J. Nowakowski: Department of Anatomy, Department of Psychiatry, University of California, San Francisco, San Francisco, CA 94158, USA
Lisa V. Goodrich: Department of Neurobiology, Harvard Medical School, Boston, MA 02115, USA
Jeanne T. Paz: Neuroscience Graduate Program, University of California, San Francisco, San Francisco, CA 94158, USA; Department of Neurology, University of California, San Francisco, San Francisco, CA 94158, USA; Gladstone Institute of Neurological Disease, San Francisco, CA 94158, USA
John L.R. Rubenstein: Nina Ireland Laboratory of Developmental Neurobiology, Department of Psychiatry, UCSF Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA 94158, USA; Neuroscience Graduate Program, University of California, San Francisco, San Francisco, CA 94158, USA; Corresponding author

Journal volume & issue: Vol. 26, no. 5
pp. 1157 – 1173.e5

Abstract

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Summary: Mafb and c-Maf transcription factor (TF) expression is enriched in medial ganglionic eminence (MGE) lineages, beginning in late-secondary progenitors and continuing into mature parvalbumin (PV+) and somatostatin (SST+) interneurons. However, the functions of Maf TFs in MGE development remain to be elucidated. Herein, Mafb and c-Maf were conditionally deleted, alone and together, in the MGE and its lineages. Analyses of Maf mutant mice revealed redundant functions of Mafb and c-Maf in secondary MGE progenitors, where they repress the generation of SST+ cortical and hippocampal interneurons. By contrast, Mafb and c-Maf have distinct roles in postnatal cortical interneuron (CIN) morphological maturation, synaptogenesis, and cortical circuit integration. Thus, Mafb and c-Maf have redundant and opposing functions at different steps in CIN development. : Using mouse genetics and ex vivo physiology studies, Pai et al. show that Mafb and c-Maf together are necessary to generate the proper numbers of parvalbumin and somatostatin GABAergic interneurons. However, in maturing interneurons, Mafb and c-Maf function divergently to control their firing properties and communication with other neurons. Keywords: somatostatin cortical interneuron, parvalbumin cortical interneuron, MAF transcription factor, interneuron fate determination, MGE

Published in Cell Reports

ISSN: 2211-1247 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Science: Biology (General)
Website: http://www.cell.com/cell-reports/home

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