An Early Cortical Progenitor-Specific Mechanism Regulates Thalamocortical Innervation
An Early Cortical Progenitor-Specific Mechanism Regulates Thalamocortical Innervation
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DOI：
10.1523/jneurosci.0226-21.2021
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发表时间：
2021-08-11
影响因子：
5.3
通讯作者：
Tole, Shubha
中科院分区：
文献类型：
--
作者：
Pal, Suranjana;Dwivedi, Deepanjali;Tole, Shubha
皮质亚板对于调节丘脑皮质感觉传入进入皮质至关重要。这些传入神经在小鼠胚胎 (E)15.5 天到达亚板，但“等待”几天，在出生后进入皮质板。我们报告说，当转录因子 LHX2 在产生板下神经元的 E11.5 皮质祖细胞中丢失时，丘脑皮质传入神经会过早、旺盛地向 E15.5 皮质内生长。胚胎突变的亚板神经元正确定位在皮质板下方，但它们在等待期间表现出改变的转录组和不成熟的电生理特性。这些皮层特异性 Lhx2 突变体中的感觉丘脑表现出萎缩，到出生后第 7 天 (P)，皮层的感觉神经支配几乎消失，导致体感桶丧失。引人注目的是，如果 LHX2 在有丝分裂后亚板神经元中丢失，这些表型不会表现出来，并且 LHX2 有丝分裂后丢失导致的亚板转录组失调与祖细胞中 LHX2 丢失时看到的情况有很大不同。这些结果证明了亚板祖细胞中的一种运作机制，对丘脑皮质轴突向皮质的生长具有深远的影响。
The cortical subplate is critical in regulating the entry of thalamocortical sensory afferents into the cortex. These afferents reach the subplate at embryonic day (E)15.5 in the mouse, but "wait" for several days, entering the cortical plate postnatally. We report that when transcription factor LHX2 is lost in E11.5 cortical progenitors, which give rise to subplate neurons, tha-lamocortical afferents display premature, exuberant ingrowth into the E15.5 cortex. Embryonic mutant subplate neurons are correctly positioned below the cortical plate, but they display an altered transcriptome and immature electrophysiological properties during the waiting period. The sensory thalamus in these cortex-specific Lhx2 mutants displays atrophy and by postnatal day (P) 7, sensory innervation to the cortex is nearly eliminated leading to a loss of the somatosensory barrels. Strikingly, these phenotypes do not manifest if LHX2 is lost in postmitotic subplate neurons, and the transcriptomic dysregu-lation in the subplate resulting from postmitotic loss of LHX2 is vastly distinct from that seen when LHX2 is lost in progeni-tors. These results demonstrate a mechanism operating in subplate progenitors that has profound consequences on the growth of thalamocortical axons into the cortex.