Pillemer G, Yelin R, Epstein M, Gont L, Frumkin Y, Yisraeli J K, Steinbeisser H, Fainsod A
Department of Cellular Biochemistry, Hebrew University Hadassah Medical School, P.O. Box 12272, Jerusalem 91120, Israel.
Mech Dev. 1998 Jun;74(1-2):133-43. doi: 10.1016/s0925-4773(98)00075-6.
Patterning of the marginal zone in the Xenopus embryo has been attributed to interactions between dorsal genes expressed in the organizer and ventral-specific genes. In this antagonistic interplay of activities, BMP-4, a gene that is not expressed in the organizer, provides a strong ventralizing signal. The Xenopus caudal type homeobox gene, Xcad-2, which is expressed around the blastopore with a gap over the dorsal lip, was analyzed as part of the ventral signal. Xcad-2 was shown to efficiently repress during early gastrula stages the dorsal genes gsc, Xnot-2, Otx-2, XFKH1 and Xlim-1, while it positively regulates the ventral genes, Xvent-1 and Xvent-2, with Xpo exhibiting a strong positive response to Xcad-2 overexpression. Xcad-2 was also capable of inducing BMP-4 expression in the organizer region. Support for a ventralizing role for Xcad-2 was obtained from co-injection experiments with the dominant negative BMP receptor which was used to block BMP-4 signaling. Under lack-of-BMP-signaling conditions Xcad-2 could still regulate dorsal and ventral gene expression and restore normal development, suggesting that it can act downstream of BMP-4 signaling or independently of it. Xcad-2 could also inhibit secondary axis formation and dorsalization induced by the dominant negative BMP receptor. Xcad-2 was also shown to efficiently reverse the dorsalizing effects of LiCl. These results place Xcad-2 as part of the ventralizing gene program which acts during early gastrula stages and can execute its ventralizing function in the absence of BMP signaling.
非洲爪蟾胚胎边缘区的模式形成被认为是组织者中表达的背侧基因与腹侧特异性基因之间相互作用的结果。在这种活动的拮抗相互作用中，组织者中不表达的基因BMP - 4提供了一个强大的腹侧化信号。非洲爪蟾尾型同源框基因Xcad - 2作为腹侧信号的一部分进行了分析，该基因在胚孔周围表达，背唇处有一个间隙。研究表明，在原肠胚早期阶段，Xcad - 2能有效抑制背侧基因gsc、Xnot - 2、Otx - 2、XFKH1和Xlim - 1，同时它正向调节腹侧基因Xvent - 1和Xvent - 2，其中Xpo对Xcad - 2过表达表现出强烈的阳性反应。Xcad - 2还能够在组织者区域诱导BMP - 4表达。通过与用于阻断BMP - 4信号传导的显性负性BMP受体进行共注射实验，获得了Xcad - 2具有腹侧化作用的证据。在缺乏BMP信号传导的条件下，Xcad - 2仍然可以调节背侧和腹侧基因的表达并恢复正常发育，这表明它可以在BMP - 4信号传导的下游起作用，或者独立于该信号传导起作用。Xcad - 2还可以抑制由显性负性BMP受体诱导的次级轴形成和背侧化。研究还表明，Xcad - 2能有效逆转LiCl的背侧化作用。这些结果表明，Xcad - 2是腹侧化基因程序的一部分，在原肠胚早期发挥作用，并且在没有BMP信号的情况下也能执行其腹侧化功能。
