MTG8 interacts with LHX6 to specify cortical interneuron subtype identity.

MTG8 interacts with LHX6 to specify cortical interneuron subtype identity.
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DOI:
10.1038/s41467-022-32898-6
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发表时间:
2022-09-05
影响因子:
16.6
通讯作者:
--
中科院分区:
综合性期刊1区
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起源于胚胎内侧神经节隆起(MGE)的皮质中间神经元在成年小鼠的大脑皮质中发现了一系列不同的亚型。这种分化的机制和亚型同一性建立的时间尚不清楚。我们发现高度保守的转录辅助因子MTG8在MGE皮质中间神经元的大亚群的发育中起关键作用,这些神经元共同表达生长抑素(SST)和神经肽Y(NPY)。MTG8与PAN-MGE转录因子LHX6相互作用,这两个因子共同作用足以促进关键的皮质间神经元亚型识别基因的表达。SST-NPY皮质间神经元的命运很早就开始了,早在中间神经元迁移到皮质之前,证明了一个早期起病的规范程序。我们的发现表明,转录辅助因子和通用谱系规范程序的修饰物可能是胚胎端脑生发区皮质神经元间异质性出现的关键。哺乳动物大脑皮质中存在着种类繁多的抑制性中间神经元。目前尚不清楚这种情况是如何在胚胎发育过程中出现的。在这里,作者确认MTG8是LHX6的辅助因子和皮质间神经元发育的新调节因子。
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. There is a large diversity of inhibitory interneurons in the mammalian cerebral cortex. How this emerges during embryogenesis remains unclear. Here, the authors identify MTG8 as a co-factor of LHX6 and a new regulator of cortical interneuron development.
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