Londin Eric R, Niemiec Jack, Sirotkin Howard I
Department of Neurobiology and Behavior, Stony Brook University, Stony Brook, NY 11794, USA.
Dev Biol. 2005 Mar 1;279(1):1-19. doi: 10.1016/j.ydbio.2004.11.016.
The ectoderm gives rise to both neural tissue and epidermis. In vertebrates, specification of the neural plate requires repression of bone morphogenetic protein (BMP) signaling in the dorsal ectoderm. The extracellular BMP antagonist Chordin and other signals from the dorsal mesoderm play important roles in this process. We utilized zebrafish mutant combinations that disrupt Chordin and mesoderm formation to reveal additional signals that contribute to the establishment of the neural domain. We demonstrate that fibroblast growth factor (FGF) signaling accounts for the additional activity in neural specification. Impeding FGF signaling results in a shift of ectodermal markers from neural to epidermal. However, following inhibition of FGF signaling, expression of anterior neural markers recovers in a Nodal-dependent fashion. Simultaneously blocking, Chordin, mesoderm formation, and FGF signaling eliminates neural marker expression during gastrula stages. We observed that FGF signaling is required for chordin expression but that it also acts via other mechanisms to repress BMP transcription during late blastula stages. Activation of FGF signaling was also able to repress BMP transcription in the absence of protein synthesis. Our results support a model in which specification of anterior neural tissue requires early FGF-mediated repression of BMP transcript levels and later activities of Chordin and mesodermal factors.
外胚层可分化为神经组织和表皮。在脊椎动物中，神经板的特化需要抑制背侧外胚层中的骨形态发生蛋白（BMP）信号传导。细胞外BMP拮抗剂Chordin和来自背侧中胚层的其他信号在此过程中发挥重要作用。我们利用破坏Chordin和中胚层形成的斑马鱼突变体组合，以揭示有助于神经区域建立的其他信号。我们证明成纤维细胞生长因子（FGF）信号传导可解释神经特化中的额外活性。阻碍FGF信号传导会导致外胚层标志物从神经型转变为表皮型。然而，在抑制FGF信号传导后，前神经标志物的表达以Nodal依赖性方式恢复。同时阻断Chordin、中胚层形成和FGF信号传导可消除原肠胚阶段的神经标志物表达。我们观察到FGF信号传导是Chordin表达所必需的，但它在囊胚后期也通过其他机制抑制BMP转录。在没有蛋白质合成的情况下，FGF信号传导的激活也能够抑制BMP转录。我们的结果支持这样一种模型，即前神经组织的特化需要早期FGF介导的BMP转录水平抑制以及后期Chordin和中胚层因子的活性。
