Nagano Takashi, Takehara Shoko, Takahashi Maiko, Aizawa Shinichi, Yamamoto Akihito
Laboratory for Vertebrate Body Plan, RIKEN Center for Developmental Biology, 2-2-3 Minatojima Minami, Chuo-ku, Kobe 650-0047, Japan.
Development. 2006 Dec;133(23):4643-54. doi: 10.1242/dev.02657. Epub 2006 Oct 25.
In vertebrate somitogenesis, FGF and Wnt signals constitute a morphogenetic gradient that controls the maturation of the presomitic mesoderm (PSM) as well as the transition to segmental units. It remains unclear, however, whether there is a regulatory mechanism that promotes the transition by a direct regulation of FGF and Wnt signaling in the PSM. Here we show that Shisa2, a member of a novel Shisa gene family, plays an essential role in segmental patterning during Xenopus somitogenesis. Shisa2 encodes an endoplasmic reticulum (ER) protein that cell-autonomously inhibits FGF and Wnt signaling by preventing the maturation and the cell-surface expression of their receptors. Shisa2 is expressed in the PSM and its knockdown caused a reduction in somite number by the delayed maturation of PSM and anterior shift of the transition; however, the phase of the segmental clock remained intact. These phenotypes were abolished by the inhibition of both FGF and Wnt signals, but by neither alone. We therefore propose that the individual inhibition of both types of signaling by the regulation of receptor maturation in the ER plays an essential role in the establishment of proper segmental patterning.
在脊椎动物体节发生过程中，成纤维细胞生长因子（FGF）和Wnt信号构成一种形态发生梯度，控制前体节中胚层（PSM）的成熟以及向节段单元的转变。然而，目前尚不清楚是否存在一种通过直接调控PSM中FGF和Wnt信号来促进这种转变的调节机制。在此，我们表明Shisa2是一个新的Shisa基因家族的成员，在非洲爪蟾体节发生过程中的节段模式形成中起关键作用。Shisa2编码一种内质网（ER）蛋白，该蛋白通过阻止其受体的成熟和细胞表面表达来细胞自主抑制FGF和Wnt信号。Shisa2在PSM中表达，其敲低导致体节数量减少，原因是PSM成熟延迟和转变向前移位；然而，节段时钟的相位保持完整。这些表型通过同时抑制FGF和Wnt信号而消除，但单独抑制其中任何一个信号均无此效果。因此，我们提出通过在内质网中调节受体成熟对这两种信号进行单独抑制，在建立正确的节段模式中起关键作用。
