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
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
