Maf and Mafb control mouse pallial interneuron fate and maturation through neuropsychiatric disease gene regulation
Abstract
Maf (c-Maf) and Mafb transcription factors (TFs) have compensatory roles in repressing somatostatin (SST+) interneuron (IN) production in medial ganglionic eminence (MGE) secondary progenitors in mice. Maf and Mafb conditional deletion (cDKO) decreases the survival of MGE-derived cortical interneurons (CINs) and changes their physiological properties. Herein, we show that (1) Mef2c and Snap25 are positively regulated by Maf and Mafb to drive IN morphological maturation; (2) Maf and Mafb promote Mef2c expression which specifies parvalbumin (PV+) INs; (3) Elmo1, Igfbp4 and Mef2c are candidate markers of immature PV+ hippocampal INs (HIN). Furthermore, Maf/Mafb neonatal cDKOs have decreased CINs and increased HINs, that express Pnoc, an HIN specific marker. Our findings not only elucidate key gene targets of Maf and Mafb that control IN development, but also identify for the first time TFs that differentially regulate CIN vs. HIN production.
Data availability
We submitted the original source data that was used for Seurat pipeline analysis to GEO under the accession number GSE144222. Readers can utilize these datasets for reanalysis and new analysis using Seurat pipeline or other customized codes for more data mining.
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Function of Mafb and c-Maf in MGE-derived interneuron developmentNCBI Gene Expression Omnibus, GSE144222.
Article and author information
Author details
Funding
National Institute of Mental Health (MH081880)
- Emily Ling-Lin Pai
- John LR Rubenstein
National Science Foundation (1608236)
- Frances S Cho
- Jeanne Paz
National Science Foundation (1144247)
- Frances S Cho
NIH Office of the Director (F31 NS111819-01A1)
- Frances S Cho
National Institute of Mental Health (MH049428)
- John LR Rubenstein
National Institute of Diabetes and Digestive and Kidney Diseases (P30DK098722)
- Emily Ling-Lin Pai
- John LR Rubenstein
NIH Office of the Director (GM134154)
- Jin Chen
National Institute of Neurological Disorders and Stroke (NS34661)
- Siavash Fazel Darbandi
- John LR Rubenstein
Simons Foundation (SFARI A133320)
- Siavash Fazel Darbandi
- John LR Rubenstein
National Institute of Neurological Disorders and Stroke (K08NS091537)
- Julia S Chu
- Mercedes F Paredes
Spectrum Health-MSU Alliance Corporation
- Daniel Vogt
National Institute of Neurological Disorders and Stroke (R01NS096369)
- Frances S Cho
- Jiapei Chen
- Jeanne Paz
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: All procedures and animal care were approved and performed in accordance with the University of California San Francisco Laboratory Animal Research Center (LARC) guidelines. All animals were handled based on the approved institutional animal care and use committee (IACUC) protocol (AN180174-01B) at the University of California San Francisco.
Reviewing Editor
- Joseph G Gleeson, Howard Hughes Medical Institute, The Rockefeller University, United States
Publication history
- Received: January 6, 2020
- Accepted: May 22, 2020
- Accepted Manuscript published: May 26, 2020 (version 1)
- Version of Record published: June 9, 2020 (version 2)
Copyright
© 2020, Pai et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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