Department of Life Sciences (Biology), Graduate School of Arts and Sciences, The University of Tokyo, 3-8-1, Komaba, Meguro-ku, Tokyo, 153-8902, Japan.
Department of Life Sciences (Biology), Graduate School of Arts and Sciences, The University of Tokyo, 3-8-1, Komaba, Meguro-ku, Tokyo, 153-8902, Japan.
Dev Biol. 2022 Aug;488:81-90. doi: 10.1016/j.ydbio.2022.05.009. Epub 2022 May 19.
Pre-placodal ectoderm (PPE), a horseshoe-shaped narrow region formed during early vertebrate development, gives rise to multiple types of sensory organs and ganglia. For PPE induction, a certain level of FGF signal activation is required. However, it is difficult to reproducibly induce the narrow region with variations in gene expression, including FGF, among individuals. An intracellular regulatory factor of FGF signaling, Dusp6, is expressed by FGF signal activation and inactivates a downstream regulator, ERK1/2, in adult tissues; however, its role in early development is not well known. Here, we reveal that Dusp6 is expressed in an FGF-dependent manner in Xenopus PPE. Gain- and loss-of-function experiments showed that Dusp6 is required for expression of a PPE gene, Six1, and patterning of adjacent regions, neural plate, and neural crest. To reveal the importance of Dusp6 in variable FGF production, we performed Dusp6 knockdown with FGF-bead implantation, which resulted in varying Six1 expression patterns. Taken together, these results suggest that Dusp6 is required for PPE formation and that it contributes to the robust patterning of PPE by mediating FGF signaling.
预置脑区外胚层(PPE),在早期脊椎动物发育过程中形成的马蹄形狭窄区域,产生多种类型的感觉器官和神经节。对于 PPE 的诱导,需要一定水平的 FGF 信号激活。然而,在个体之间,包括 FGF 在内的基因表达存在变化,难以重现诱导狭窄区域。FGF 信号转导的细胞内调节因子 Dusp6 由 FGF 信号激活表达,并在成年组织中使下游调节剂 ERK1/2 失活;然而,其在早期发育中的作用尚不清楚。在这里,我们揭示了 Dusp6 在 Xenopus PPE 中以 FGF 依赖的方式表达。获得和丧失功能实验表明,Dusp6 对于 PPE 基因 Six1 的表达和相邻区域、神经板和神经嵴的模式形成是必需的。为了揭示 Dusp6 在可变 FGF 产生中的重要性,我们进行了 Dusp6 的敲低实验,并用 FGF 珠植入,导致 Six1 表达模式的变化。总之,这些结果表明 Dusp6 对于 PPE 的形成是必需的,并且通过介导 FGF 信号转导有助于 PPE 的稳健模式形成。