Wolfson Institute for Biomedical Research, University College London, Gower Street, London, WC1E 6BT, UK.
Biomedical Sciences Research Center "Alexander Fleming", Vari, Greece.
Nat Commun. 2022 Sep 5;13(1):5217. doi: 10.1038/s41467-022-32898-6.
Cortical interneurons originating in the embryonic medial ganglionic eminence (MGE) diverge into a range of different subtypes found in the adult mouse cerebral cortex. The mechanisms underlying this divergence and the timing when subtype identity is set up remain unclear. We identify the highly conserved transcriptional co-factor MTG8 as being pivotal in the development of a large subset of MGE cortical interneurons that co-expresses Somatostatin (SST) and Neuropeptide Y (NPY). MTG8 interacts with the pan-MGE transcription factor LHX6 and together the two factors are sufficient to promote expression of critical cortical interneuron subtype identity genes. The SST-NPY cortical interneuron fate is initiated early, well before interneurons migrate into the cortex, demonstrating an early onset specification program. Our findings suggest that transcriptional co-factors and modifiers of generic lineage specification programs may hold the key to the emergence of cortical interneuron heterogeneity from the embryonic telencephalic germinal zones.
起源于胚胎内侧神经节隆起（MGE）的皮质中间神经元分化为成年小鼠大脑皮层中存在的一系列不同亚型。导致这种分化的机制以及亚型身份设定的时间尚不清楚。我们发现高度保守的转录共因子 MTG8 是一大类 MGE 皮质中间神经元发育的关键，这些神经元共同表达生长抑素（SST）和神经肽 Y（NPY）。MTG8 与泛 MGE 转录因子 LHX6 相互作用，这两个因子共同足以促进关键皮质中间神经元亚型身份基因的表达。SST-NPY 皮质中间神经元命运在中间神经元迁移到皮层之前很早就开始了，这表明存在一个早期起始的特化程序。我们的研究结果表明，通用谱系特化程序的转录共因子和修饰因子可能是胚胎端脑生殖区皮质中间神经元异质性出现的关键。
