<i>Maf</i> and <i>Mafb</i> control mouse pallial interneuron fate and maturation through neuropsychiatric disease gene regulation.

Abstract

<i>​Maf</i> (<i>c-Maf</i>) and <i>Mafb</i> transcription factors (TFs) have compensatory roles in repressing somatostatin (SST⁺) interneuron (IN) production in medial ganglionic eminence (MGE) secondary progenitors in mice. <i>Maf</i> and <i>Mafb</i> conditional deletion (cDKO) decreases the survival of MGE-derived cortical interneurons (CINs) and changes their physiological properties. Herein, we show that (1) <i>Mef2c</i> and <i>Snap25</i> are positively regulated by <i>Maf</i> and <i>Mafb</i> to drive IN morphological maturation; (2) <i>Maf</i> and <i>Mafb</i> promote <i>Mef2c</i> expression which specifies parvalbumin (PV⁺) INs; (3) <i>Elmo1</i>, <i>Igfbp4</i> and <i>Mef2c</i> are candidate markers of immature PV⁺ hippocampal INs (HIN). Furthermore, <i>Maf</i>/<i>Mafb</i> neonatal cDKOs have decreased CINs and increased HINs, that express <i>Pnoc</i>, an HIN specific marker. Our findings not only elucidate key gene targets of <i>Maf</i> and <i>Mafb</i> that control IN development, but also identify for the first time TFs that differentially regulate CIN vs. HIN production.