Maf and Mafb control mouse pallial interneuron fate and maturation through neuropsychiatric disease gene regulation

Elife. 2020 May 26;9:e54903. doi: 10.7554/eLife.54903.

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.

Keywords: MGE; developmental biology; hippocampal interneuron; interneuron development; maf transcription factor; mouse; neuroscience; parvalbumin.

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

  • Animals
  • Female
  • Gene Expression Regulation*
  • Interneurons / metabolism*
  • MEF2 Transcription Factors / metabolism
  • MafB Transcription Factor / physiology*
  • Mice
  • Nervous System Diseases / etiology
  • Pregnancy
  • Protein Precursors / genetics
  • Proto-Oncogene Proteins c-maf / physiology*
  • Receptors, CXCR4 / metabolism
  • Receptors, Opioid / genetics
  • Single-Cell Analysis
  • Synaptosomal-Associated Protein 25 / metabolism
  • Transcriptome

Substances

  • CXCR4 protein, mouse
  • MEF2 Transcription Factors
  • Maf protein, mouse
  • MafB Transcription Factor
  • Mafb protein, mouse
  • Mef2c protein, mouse
  • Protein Precursors
  • Proto-Oncogene Proteins c-maf
  • Receptors, CXCR4
  • Receptors, Opioid
  • Snap25 protein, mouse
  • Synaptosomal-Associated Protein 25
  • prepronociceptin

Associated data

  • GEO/GSE144222