Maf and Mafb control mouse pallial interneuron fate and maturation through neuropsychiatric disease gene regulation
Year: 2020
Type: article
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.
Source: eLife
DOI: 10.7554/elife.54903
Language: English
Subfield: Developmental Neuroscience
Field: Neuroscience
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $2,500
Funders: National Science Foundation, Simons Foundation, Jane Coffin Childs Memorial Fund for Medical Research, Gladstone Institutes, Simons Foundation Autism Research Initiative, National Institutes of Health, University of California, San Francisco, Nutrition Obesity Research Center, University of North Carolina, National Institute of Mental Health, NIH Office of the Director, National Institute of General Medical Sciences, National Institute of Diabetes and Digestive and Kidney Diseases, National Institute of Neurological Disorders and Stroke
Awards: G1612028174, G2281520231, Determining the role of dysregulated GABA uptake by reactive astrocytes in thalamic circuit hyperexcitability and seizures, G2899792735, G2965820276, G3064501752, G3587456789, G3595868160, G3596311957, US-French Research Proposal: Experimental and Theoretical Investigation of the Multi-Scale Emergence of Parametric Working Memory in Prefrontal Cortex Recurrent Networks, G4480946400, G4577585030, G4805411423, Genetic Studies of Cortex Structure and Development, G6090737961, Graduate Research Fellowship Program (GRFP), G6383384417, G6480478911, G661255219, G701148663, G7104779986, G716694877, G738160294, G740445058, UCSF Nutrition Obesity Research Center, G8078861302, G8293452648, G8818828807, G9000023660, G9000030165, G9000204047, G9000264222, G9000325660, G977768287
OpenAlex ID: W3029495913