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.
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.
Cell Rep. 2019 Jan 29;26(5):1157-1173.e5. doi: 10.1016/j.celrep.2019.01.031.
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.
Mafb 和 c-Maf 转录因子(TF)表达在中脑神经节隆起(MGE)谱系中富集,从晚期次代祖细胞开始,并持续存在于成熟的 parvalbumin(PV)和 somatostatin(SST)中间神经元中。然而,Maf TFs 在 MGE 发育中的功能仍有待阐明。在此,Mafb 和 c-Maf 分别在 MGE 及其谱系中条件性缺失。对 Maf 突变小鼠的分析表明,Mafb 和 c-Maf 在次级 MGE 祖细胞中具有冗余功能,它们抑制 SST 皮质和海马中间神经元的产生。相比之下,Mafb 和 c-Maf 在出生后皮质中间神经元(CIN)形态成熟、突触发生和皮质回路整合中具有不同的作用。因此,Mafb 和 c-Maf 在 CIN 发育的不同步骤中具有冗余和相反的功能。