Moore K B, Moody S A
Department of Anatomy and Cell Biology, Institute for Biomedical Sciences, The George Washington University Medical Center, 2300 Eye Street NW, Ross Hall, Washington, DC, 20037, USA.
Dev Biol. 1999 Aug 1;212(1):25-41. doi: 10.1006/dbio.1999.9338.
An individual retina descends from a restricted and invariant group of nine animal blastomeres at the 32-cell stage. We tested which molecular signaling pathways are responsible for the competence of animal blastomeres to contribute to the retina. Inactivation of activin/Vg1 or fibroblast growth factor (FGF) signaling by expression of dominant-negative receptors does not prevent an animal blastomere from contributing to the retina. However, increasing bone morphogenetic protein (BMP) signaling in the retina-producing blastomeres significantly reduces their contribution. Conversely, reducing BMP signaling by expression of a dominant-negative BMP receptor or Noggin allows other animal blastomeres to contribute to the retina. Thus, the initial step in the retinal lineage is regulated by position within the BMP/Noggin field of epidermal versus neural induction. Vegetal tier blastomeres, in contrast, cannot contribute to the retina even when given access to the appropriate position and signaling fields by transplantation to the dorsal animal pole. We tested whether expression of molecules within the mesoderm inducing (activin, FGF), mesoderm-modifying (Wnt), or neural-inducing (BMP, Noggin) pathways impart a retinal fate on vegetal cell descendants. None of these, several of which induce secondary head structures, caused vegetal cells to contribute to retina. This was true even if the injected blastomeres were transplanted to the dorsal animal pole. Two pathways that specifically induce head tissues also were investigated. The simultaneous blockade of Wnt and BMP signaling, which results in the formation of a complete secondary axis with head and eyes, did not cause the vegetal clone to give rise to retina. However, Cerberus, a secreted protein that also induces an ectopic head with eyes, redirected vegetal progeny into the retina. These experiments indicate that vegetal blastomere incompetence to express a retinal fate is not due to a lack of components of known signaling pathways, but relies on a specific pathway of head induction.
单个视网膜起源于32细胞期由9个动物卵裂球组成的一个受限且不变的群体。我们测试了哪些分子信号通路决定了动物卵裂球形成视网膜的能力。通过表达显性负性受体使激活素/Vg1或成纤维细胞生长因子（FGF）信号失活，并不会阻止动物卵裂球形成视网膜。然而，增加产生视网膜的卵裂球中的骨形态发生蛋白（BMP）信号会显著减少它们形成视网膜的能力。相反，通过表达显性负性BMP受体或Noggin来降低BMP信号，能使其他动物卵裂球形成视网膜。因此，视网膜谱系的起始步骤受表皮与神经诱导的BMP/Noggin场中的位置调控。相比之下，植物层卵裂球即使通过移植到背侧动物极而处于合适的位置和信号场中，也无法形成视网膜。我们测试了中胚层诱导（激活素、FGF）、中胚层修饰（Wnt）或神经诱导（BMP、Noggin）通路中的分子表达是否能赋予植物细胞后代视网膜命运。这些分子中没有一个能使植物细胞形成视网膜，其中有几个会诱导次生头部结构，即便将注射了这些分子的卵裂球移植到背侧动物极也是如此。我们还研究了两条特异性诱导头部组织的通路。同时阻断Wnt和BMP信号会导致形成带有头部和眼睛的完整次生轴，但并不会使植物克隆形成视网膜。然而，同样能诱导带有眼睛的异位头部的分泌蛋白Cerberus，却能使植物后代形成视网膜。这些实验表明，植物卵裂球无法表达视网膜命运并非由于缺乏已知信号通路的成分，而是依赖于一条特定的头部诱导通路。
