Takahashi Chika, Suzuki Toshiyasu, Nishida Eisuke, Kusakabe Morioh
Department of Cell and Developmental Biology, Graduate School of Biostudies, Kyoto University, Kyoto, Japan.
Int J Dev Biol. 2012;56(5):393-402. doi: 10.1387/ijdb.113333ct.
The FGF pathway regulates a variety of developmental processes in animals through activation and/or repression of numerous target genes. Here we have identified a Xenopus homolog of potassium channel tetramerization domain containing 15 (KCTD15) as an FGF-repressed gene. Kctd15 expression is first detected at the gastrula stage and gradually increases until the tadpole stage. Whole-mount in situ hybridization reveals that the spatial expression of kctd15 is tightly regulated during early embryogenesis. While kctd15 is uniformly expressed throughout the presumptive ectoderm at the early gastrula stage, its expression becomes restricted to the non-neural ectoderm and is excluded from the neural plate at the early neurula stage. At the mid-neurula stage, kctd15 shows a more restricted distribution pattern in regions that are located at the anterior, lateral or medial edge of the neural fold, including the preplacodal ectoderm, the craniofacial neural crest and the prospective roof plate. At the tailbud stage, kctd15 expression is mainly detected in neural crest- or placode-derived tissues that are located around the eye, including the mandibular arch, trigeminal ganglia and the olfactory placode. FGF represses kctd15 expression in ectodermal explants, and the inhibition of FGF receptor with a chemical compound dramatically expands the region expressing kctd15 in whole embryos. Dorsal depletion of kctd15 in Xenopus embryos leads to bent axes with reduced head structures, defective eyes and abnormal somites, while ventral depletion causes defects in ventral and caudal morphologies. These results suggest that kctd15 is an FGF-repressed ectodermal gene required for both dorsal and ventral development.
成纤维细胞生长因子(FGF)信号通路通过激活和/或抑制众多靶基因来调控动物的多种发育过程。在此,我们鉴定出非洲爪蟾中一个含钾通道四聚化结构域15(KCTD15)的同源物,它是一个受FGF抑制的基因。Kctd15的表达最早在原肠胚期被检测到,并逐渐增加直至蝌蚪期。整体原位杂交显示,kctd15在早期胚胎发育过程中的空间表达受到严格调控。在原肠胚早期,kctd15在整个预定外胚层中均匀表达,而在神经胚早期,其表达局限于非神经外胚层,且被排除在神经板之外。在神经胚中期,kctd15在位于神经褶前缘、侧缘或内侧缘的区域呈现出更局限的分布模式,包括前板外胚层、颅面神经嵴和预期的顶板。在尾芽期,kctd15表达主要在眼周的神经嵴或基板衍生组织中检测到,包括下颌弓、三叉神经节和嗅基板。FGF在外胚层外植体中抑制kctd15的表达,用一种化合物抑制FGF受体可显著扩大kctd15在整个胚胎中的表达区域。在非洲爪蟾胚胎中,kctd15的背侧缺失会导致轴弯曲,头部结构减小,眼睛缺陷和体节异常,而腹侧缺失则会导致腹侧和尾部形态缺陷。这些结果表明,kctd15是一个受FGF抑制的外胚层基因,对背侧和腹侧发育均必不可少。