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

doi:10.1016/j.celrep.2019.01.031

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

Cell Rep. 2019 Jan 29;26(5):1157-1173.e5. doi: 10.1016/j.celrep.2019.01.031.

Authors

Affiliations

¹ 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.
² 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.
³ 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.
⁴ Nina Ireland Laboratory of Developmental Neurobiology, Department of Psychiatry, UCSF Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA 94158, USA.
⁵ Department of Neurology, University of California, San Francisco, San Francisco, CA 94158, USA; Gladstone Institute of Neurological Disease, San Francisco, CA 94158, USA.
⁶ Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA.
⁷ Department of Anatomy, Department of Psychiatry, University of California, San Francisco, San Francisco, CA 94158, USA.
⁸ Department of Neurobiology, Harvard Medical School, Boston, MA 02115, USA.
⁹ 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. Electronic address: john.rubenstein@ucsf.edu.

Abstract

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.

Keywords: MAF transcription factor; MGE; interneuron fate determination; parvalbumin cortical interneuron; somatostatin cortical interneuron.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

Action Potentials
Animals
Animals, Newborn
Apoptosis
Cell Lineage*
Cell Membrane / metabolism
Cell Movement
Cell Proliferation
Cerebral Cortex / metabolism*
Hippocampus / metabolism
Interneurons / metabolism*
MafB Transcription Factor / metabolism*
Median Eminence / metabolism
Mice, Knockout
Neurites / metabolism
Neurogenesis
Parvalbumins / metabolism
Proto-Oncogene Proteins c-maf / metabolism*
Somatostatin / metabolism
Synapses / metabolism

Substances

MafB Transcription Factor
Mafb protein, mouse
Parvalbumins
Proto-Oncogene Proteins c-maf
Somatostatin

Abstract

Publication types

MeSH terms

Substances

Grants and funding