Shimoda Marine Research Center, University of Tsukuba, 5-10-1 Shimoda, Shizuoka 415-0025, Japan.
Development. 2011 Oct;138(19):4233-43. doi: 10.1242/dev.069856. Epub 2011 Aug 18.
Partitioning ectoderm precisely into neurogenic and non-neurogenic regions is an essential step for neurogenesis of almost all bilaterian embryos. Although it is widely accepted that antagonism between BMP and its inhibitors primarily sets up the border between these two types of ectoderm, it is unclear how such extracellular, diffusible molecules create a sharp and precise border at the single-cell level. Here, we show that Fez, a zinc finger protein, functions as an intracellular factor attenuating BMP signaling specifically within the neurogenic region at the anterior end of sea urchin embryos, termed the animal plate. When Fez function is blocked, the size of this neurogenic ectoderm becomes smaller than normal. However, this reduction is rescued in Fez morphants simply by blocking BMP2/4 translation, indicating that Fez maintains the size of the animal plate by attenuating BMP2/4 function. Consistent with this, the gradient of BMP activity along the aboral side of the animal plate, as measured by pSmad1/5/8 levels, drops significantly in cells expressing Fez and this steep decline requires Fez function. Our data reveal that this neurogenic ectoderm produces an intrinsic system that attenuates BMP signaling to ensure the establishment of a stable, well-defined neural territory, the animal plate.
精确地将外胚层划分为神经发生和非神经发生区域是几乎所有两侧胚胎神经发生的关键步骤。虽然人们普遍认为 BMP 与其抑制剂之间的拮抗作用主要决定了这两种类型的外胚层之间的边界，但尚不清楚这种细胞外可扩散分子如何在单细胞水平上形成一个锐利而精确的边界。在这里，我们表明锌指蛋白 Fez 作为一种细胞内因子，特异性地在海胆胚胎前端的神经发生区域（称为动物帽）内减弱 BMP 信号。当 Fez 功能被阻断时，这个神经发生外胚层的大小会小于正常大小。然而，在 Fez 突变体中，通过阻断 BMP2/4 翻译，这种减少可以得到挽救，这表明 Fez 通过减弱 BMP2/4 功能来维持动物帽的大小。与这一结果一致的是，通过测量 pSmad1/5/8 水平，在表达 Fez 的细胞中，动物帽沿口后侧的 BMP 活性梯度显著下降，而这种陡峭下降需要 Fez 功能。我们的数据揭示了这种神经发生外胚层产生了一种内在的系统，减弱了 BMP 信号，以确保建立一个稳定、明确的神经区域，即动物帽。
