Gore Aniket V, Maegawa Shingo, Cheong Albert, Gilligan Patrick C, Weinberg Eric S, Sampath Karuna
Vertebrate Development Group, Temasek Life Sciences Laboratory, 1 Research Link, 117604 Singapore.
Nature. 2005 Dec 15;438(7070):1030-5. doi: 10.1038/nature04184.
A central question in the development of multicellular organisms pertains to the timing and mechanisms of specification of the embryonic axes. In many organisms, specification of the dorsoventral axis requires signalling by proteins of the Transforming growth factor-beta and Wnt families. Here we show that maternal transcripts of the zebrafish Nodal-related morphogen, Squint (Sqt), can localize to two blastomeres at the four-cell stage and predict the dorsal axis. Removal of cells containing sqt transcripts from four-to-eight-cell embryos or injection of antisense morpholino oligonucleotides targeting sqt into oocytes can cause a loss of dorsal structures. Localization of sqt transcripts is independent of maternal Wnt pathway function and requires a highly conserved sequence in the 3' untranslated region. Thus, the dorsoventral axis is apparent by early cleavage stages and may require the maternally encoded morphogen Sqt and its associated factors. Because the 3' untranslated region of the human nodal gene can also localize exogenous sequences to dorsal cells, this mechanism may be evolutionarily conserved.
多细胞生物发育过程中的一个核心问题涉及胚胎轴特化的时间和机制。在许多生物中，背腹轴的特化需要转化生长因子-β和Wnt家族的蛋白质进行信号传导。我们在此表明，斑马鱼Nodal相关形态发生素Squint（Sqt）的母体转录本在四细胞期可定位于两个卵裂球，并预测背轴。从四细胞到八细胞胚胎中去除含有sqt转录本的细胞，或将靶向sqt的反义吗啉代寡核苷酸注射到卵母细胞中，会导致背侧结构缺失。sqt转录本的定位独立于母体Wnt信号通路功能，并且需要3'非翻译区中一个高度保守的序列。因此，背腹轴在早期卵裂阶段就很明显，可能需要母体编码的形态发生素Sqt及其相关因子。由于人类nodal基因的3'非翻译区也可将外源序列定位于背侧细胞，这种机制可能在进化上是保守的。
