Early dorsomedial tissue interactions regulate gyrification of distal neocortex
Early dorsomedial tissue interactions regulate gyrification of distal neocortex
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DOI：
10.1038/s41467-019-12913-z
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发表时间：
2019-11-15
影响因子：
16.6
通讯作者：
Millen, Kathleen J.
中科院分区：
文献类型：
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作者：
Chizhikov, Victor V.;Iskusnykh, Igor Y.;Millen, Kathleen J.
新皮层脑回化的程度是一个物种认知能力的重要决定因素，但调节皮层脑回化的机制知之甚少。我们揭示了这一过程的远程调节起源于端脑背中线，分泌的BMPs的水平维持在神经上皮细胞和上覆间充质的因素。在小鼠中，分别在中线神经上皮和间充质中选择性表达的转录因子Lmx 1a和Lmx 1b的组合损失导致背中线Bmp信号在早期神经管阶段下降。这改变了背中线皮质边缘的空间和时间Wnt信号传导谱，这反过来又导致远端新皮质的回转。我们的研究揭示了早期间充质-神经上皮的相互作用，对新皮质脑回形成有长期影响，并表明小鼠无脑回畸形通过背中线发育和信号传导的冗余遗传调节而积极维持。
The extent of neocortical gyrification is an important determinant of a species' cognitive abilities, yet the mechanisms regulating cortical gyrification are poorly understood. We uncover long-range regulation of this process originating at the telencephalic dorsal midline, where levels of secreted Bmps are maintained by factors in both the neuroepithelium and the overlying mesenchyme. In the mouse, the combined loss of transcription factors Lmx1a and Lmx1b, selectively expressed in the midline neuroepithelium and the mesenchyme respectively, causes dorsal midline Bmp signaling to drop at early neural tube stages. This alters the spatial and temporal Wnt signaling profile of the dorsal midline cortical hem, which in turn causes gyrification of the distal neocortex. Our study uncovers early mesenchymal-neuroepithelial interactions that have long-range effects on neocortical gyrification and shows that lissencephaly in mice is actively maintained via redundant genetic regulation of dorsal midline development and signaling.