Nomura Tadashi, Gotoh Hitoshi, Kiyonari Hiroshi, Ono Katsuhiko
Developmental Neurobiology, INAMORI Memorial Building, Kyoto Prefectural University of Medicine, Kyoto, Japan.
Laboratory for Animal Resources and Genetic Engineering, RIKEN Center for Biosystems Dynamics Research, Kobe, Japan.
Front Neurosci. 2022 Mar 23;16:811689. doi: 10.3389/fnins.2022.811689. eCollection 2022.
Temporal control of neurogenesis is central for the development and evolution of species-specific brain architectures. The balance between progenitor expansion and neuronal differentiation is tightly coordinated by cell-intrinsic and cell-extrinsic cues. Wnt signaling plays pivotal roles in the proliferation and differentiation of neural progenitors in a temporal manner. However, regulatory mechanisms that adjust intracellular signaling amplitudes according to cell fate progression remain to be elucidated. Here, we report the transcriptional controls of β, a critical regulator of Wnt signaling, in the developing mouse neocortex. β expression was higher in ventricular neural progenitors, while it gradually declined in differentiated neurons. We identified active -regulatory module (CRM) of β that responded to cell type-specific transcription factors, such as Sox2, Sox9, and Neurogenin2. Furthermore, we found extensive conservation of the CRM among mammals but not in non-mammalian amniotes. Our data suggest that a mammalian-specific CRM drives the cell type-specific activity of β to fine tune Wnt signaling, which contributes to the tight control of neurogenesis during neocortical development.
神经发生的时间控制对于物种特异性脑结构的发育和进化至关重要。祖细胞扩增与神经元分化之间的平衡由细胞内在和外在信号紧密协调。Wnt信号通路以时间依赖性方式在神经祖细胞的增殖和分化中发挥关键作用。然而，根据细胞命运进程调节细胞内信号幅度的调控机制仍有待阐明。在此，我们报道了在发育中的小鼠新皮层中，Wnt信号通路关键调节因子β的转录调控。β在脑室神经祖细胞中表达较高，而在分化的神经元中逐渐下降。我们鉴定出了β的活性调控模块（CRM），它对细胞类型特异性转录因子如Sox2、Sox9和Neurogenin2有反应。此外，我们发现该CRM在哺乳动物中广泛保守，但在非哺乳类羊膜动物中则不然。我们的数据表明，一个哺乳动物特异性的CRM驱动β的细胞类型特异性活性，以微调Wnt信号通路，这有助于在新皮层发育过程中对神经发生进行严格控制。
