后脑,从神经管扩张的前端发展而来,可以分化为中脑和髓脑,不同的大小和功能。已知中脑-后脑边界(MHB)和后脑脊髓脑/腹侧中线(HMVM)是前后脑和脊髓脑的祖细胞的来源,分别。然而,在这些结构中调节后脑形态发生的分子网络仍不清楚。在这项研究中,我们表明rb1在斑马鱼的MHB和HMVM上高表达。在小鼠和斑马鱼中敲除rb1会导致后脑神经元过度增殖而增大。进一步的研究表明,Rb1通过抑制后脑发育必需转录因子Gbx1/Gbx2的表达来控制后脑形态发生,通过其分别与E2f3/Hdac1的结合。有趣的是,我们发现Gbx1和Gbx2在不同类型的后脑神经元中表达,提示在后脑形态发生中的不同作用。总之,我们的研究通过调节E2f3-Gbx1轴和Hdac1-Gbx2轴阐明了RB1在后脑神经细胞增殖和形态发生中的特定作用。这些发现为探索不同脑区神经元的差异增殖提供了研究范式。
The
hindbrain, which develops from the anterior end of the neural tube expansion, can differentiate into the metencephalon and myelencephalon, with varying sizes and functions. The midbrain-
hindbrain boundary (MHB) and
hindbrain myelencephalon/ventral midline (HMVM) are known to be the source of the progenitors for the anterior
hindbrain and myelencephalon, respectively. However, the molecular networks regulating hindbrain morphogenesis in these structures remain unclear. In this study, we show that retinoblastoma 1 (rb1) is highly expressed at the MHB and HMVM in zebrafish. Knocking out rb1 in mice and zebrafish results in an enlarged
hindbrain due to
hindbrain neuronal hyperproliferation. Further study reveals that Rb1 controls the hindbrain morphogenesis by suppressing the expression of Gbx1/Gbx2, essential transcription factors for hindbrain development, through its binding to E2f3/Hdac1, respectively. Interestingly, we find that Gbx1 and Gbx2 are expressed in different types of hindbrain neurons, suggesting distinct roles in
hindbrain morphogenesis. In summary, our study clarifies the specific role of RB1 in hindbrain neural cell proliferation and morphogenesis by regulating the E2f3-Gbx1 axis and the Hdac1-Gbx2 axis. These findings provide a research paradigm for exploring the differential proliferation of neurons in various brain regions.