Division of Biological Science, Graduate School of Science, Nagoya University, Nagoya, Aichi, Japan.
Dev Dyn. 2021 Nov;250(11):1618-1633. doi: 10.1002/dvdy.371. Epub 2021 May 24.
Although the cell cycle and cell differentiation should be coordinately regulated to generate a variety of neurons in the brain, the molecules that are involved in this coordination still remain largely unknown. In this study, we analyzed the roles of a nuclear protein Cfdp1, which is thought to be involved in chromatin remodeling, in zebrafish neurogenesis.
Zebrafish cfdp1 mutants maintained the progenitors of granule cells (GCs) in the cerebellum, but showed defects in their differentiation to GCs. cfdp1 mutants showed an increase in phospho-histone 3 (pH 3)-positive cells and apoptotic cells, as well as a delayed cell cycle transition from the G2 to the M phase in the cerebellum. The inhibition of tp53 prevented apoptosis but not GC differentiation in the cfdp1 mutant cerebellum. A similar increase in apoptotic cells and pH 3-positive cells, and defective cell differentiation, were observed in the cfdp1 mutant retina. Although mitotic spindles formed, mitosis was blocked before anaphase in both the cerebellum and retina of cfdp1 mutant larvae. Furthermore, expression of the G2/mitotic-specific cyclin B1 gene increased in the cfdp1 mutant cerebellum.
Our findings suggest that Cfdp1 regulates the cell cycle of neural progenitors, thereby promoting neural differentiation in the brain.
尽管细胞周期和细胞分化应该协调调控以生成大脑中的各种神经元，但参与这种协调的分子在很大程度上仍然未知。在这项研究中，我们分析了核蛋白 Cfdp1 的作用，该蛋白被认为参与染色质重塑，在斑马鱼神经发生中。
斑马鱼 cfdp1 突变体维持小脑颗粒细胞 (GC) 的祖细胞，但在分化为 GC 时存在缺陷。cfdp1 突变体表现出磷酸化组蛋白 3 (pH3) 阳性细胞和凋亡细胞增加，以及小脑中细胞周期从 G2 向 M 期的过渡延迟。Tp53 的抑制可防止凋亡，但不能防止 cfdp1 突变体小脑中的 GC 分化。在 cfdp1 突变体视网膜中观察到类似的凋亡细胞和 pH3 阳性细胞增加以及细胞分化缺陷。尽管有丝分裂纺锤体形成，但 cfdp1 突变体幼虫的小脑和视网膜中的有丝分裂在后期前被阻断。此外，cfdp1 突变体小脑中 G2/有丝分裂特异性细胞周期蛋白 B1 基因的表达增加。
我们的发现表明 Cfdp1 调节神经祖细胞的细胞周期，从而促进大脑中的神经分化。
