The seat of human intelligence is the human cerebral cortex, which is responsible for our exceptional cognitive abilities. Identifying principles that lead to the development of the large-sized human cerebral cortex will shed light on what makes the human brain and species so special. The remarkable increase in the number of human cortical pyramidal neurons and the size of the human cerebral cortex is mainly because human cortical radial glial cells, primary neural stem cells in the cortex, generate cortical pyramidal neurons for more than 130 days, whereas the same process takes only about 7 days in mice. The molecular mechanisms underlying this difference are largely unknown. Here, we found that BMP7 is expressed by increasing numbers of cortical radial glial cells during mammalian evolution (mouse, ferret, monkey, man). BMP7 expression in cortical radial glial cells promotes neurogenesis, inhibits gliogenesis, and thereby increases the length of the neurogenic period, whereas SHH signaling promotes cortical gliogenesis. We demonstrate that BMP7 signaling and SHH signaling mutually inhibit each other through regulation of GLI3 repressor formation. We propose that BMP7 drives the evolutionary expansion of the mammalian cortex by increasing the length of the neurogenic period.

中文翻译：

---

BMP7 在哺乳动物皮质放射状神经胶质细胞中的表达增加了神经发生期的长度。

人类智力的基础是人类大脑皮层，它负责我们非凡的认知能力。确定导致大型人类大脑皮层发育的原理将阐明是什么让人类大脑和物种如此特别。人类皮质锥体神经元数量和大脑皮层体积的显着增加主要是因为人类皮质放射状胶质细胞，即皮质中的原代神经干细胞，产生皮质锥体神经元的时间超过130天，而同样的过程在老鼠身上只需要大约 7 天。这种差异背后的分子机制在很大程度上是未知的。在这里，我们发现 BMP7 在哺乳动物进化过程中（小鼠、雪貂、猴子、人）通过增加皮质放射状神经胶质细胞的数量来表达。BMP7 在皮质放射状神经胶质细胞中的表达促进神经发生，抑制神经胶质生成，从而增加神经发生期的长度，而 SHH 信号转导促进皮质神经胶质生成。我们证明 BMP7 信号和 SHH 信号通过调节 GLI3 阻遏物形成相互抑制。我们提出 BMP7 通过增加神经源期的长度来驱动哺乳动物皮层的进化扩展。