Bing Jie, Sun Jing, Zhao Rui, Sun Lina, Xi Chao, Liu Jin, Zhang Xinwen, Zeng Shaoju
Beijing, Key Laboratory of Gene Resource and Molecular Development, Beijing Normal University, Beijing, China.
Hainan, Institute of Science and Technology, Haikou, China.
Dev Neurobiol. 2023 Jul-Sep;83(5-6):157-166. doi: 10.1002/dneu.22920. Epub 2023 Jul 11.
There is obvious sexual dimorphism in the song control system of songbirds. In the higher vocal center (HVC), cell proliferation and neuronal differentiation contribute to the net addition of neurons. However, the mechanism underlying these changes is unclear. Given that Wnt, Bmp, and Notch pathways are involved in cell proliferation and neuronal differentiation, no reports are available to study the role of the three pathways in the song control system. To address the issue, we studied cell proliferation in the ventricle zone overlying the developing HVC and neural differentiation within the HVC of Bengalese finches (Lonchura striata) at posthatching day 15 when HVC progenitor cells are generated on a large scale and differentiate into neurons, after Wnt and Bmp pathways were activated by using a pharmacological agonist (LiCl) or Bmp4, respectively, and the Notch pathway was inhibited by an inhibitor (N-[N-(3,5-difluorophenacetyl)-l-alanyl]-S-phenylglycine t-butyl ester), DAPT). The results indicated that both cell proliferation and neural differentiation toward HVC neurons increased significantly after activation of the Wnt signaling pathway or inhibition of the Notch signaling pathway. Although cell proliferation was increased, neural differentiation was inhibited after treatment with Bmp4. There was obvious synergetic enhancement in the number of proliferating cells after the coregulation of two or three signaling pathways. In addition, synergetic enhancement was also found in the Wnt and Notch pathways in neural differentiation toward neurons within HVC. These results suggest that the three signaling pathways are involved in cell proliferation and neural differentiation of HVC.
鸣禽的发声控制系统存在明显的两性差异。在高级发声中枢（HVC）中，细胞增殖和神经元分化导致神经元的净增加。然而，这些变化背后的机制尚不清楚。鉴于Wnt、Bmp和Notch信号通路参与细胞增殖和神经元分化，目前尚无关于这三条信号通路在发声控制系统中作用的研究报道。为了解决这个问题，我们研究了在孵化后第15天，孟加拉雀（纹背文鸟）发育中的HVC上方脑室区的细胞增殖以及HVC内的神经分化情况，此时HVC祖细胞大量产生并分化为神经元，分别使用药理激动剂（氯化锂）激活Wnt和Bmp信号通路，以及使用抑制剂（N-[N-(3,5-二氟苯乙酰基)-L-丙氨酰基]-S-苯甘氨酸叔丁酯，DAPT）抑制Notch信号通路。结果表明，激活Wnt信号通路或抑制Notch信号通路后，向HVC神经元的细胞增殖和神经分化均显著增加。虽然用Bmp4处理后细胞增殖增加，但神经分化受到抑制。两条或三条信号通路共同调节后，增殖细胞数量有明显的协同增强。此外，在向HVC内神经元的神经分化过程中Wnt和Notch信号通路也发现有协同增强。这些结果表明，这三条信号通路参与了HVC的细胞增殖和神经分化。
