Nambiar Roopa M, Henion Paul D
Molecular, Cellular and Developmental Biology Program, Center for Molecular Neurobiology, Ohio State University, Columbus, OH 43210, USA.
Dev Biol. 2004 Mar 1;267(1):165-80. doi: 10.1016/j.ydbio.2003.11.019.
The establishment of the vertebrate body plan involves patterning of the ectoderm, mesoderm, and endoderm along the dorsoventral and antero-posterior axes. Interactions among numerous signaling molecules from several multigene families, including Wnts, have been implicated in regulating these processes. Here we provide evidence that the zebrafish colgate(b382) (col) mutation results in increased Wnt signaling that leads to defects in dorsal and anterior development. col mutants display early defects in dorsoventral patterning manifested by a decrease in the expression of dorsal shield-specific markers and ectopic expression of ventrolaterally expressed genes during gastrulation. In addition to these early patterning defects, col mutants display a striking regional posteriorization within the neuroectoderm, resulting in a reduction in anterior fates and an expansion of posterior fates within the forebrain and midbrain-hindbrain regions. We are able to correlate these phenotypes to the overactivation of Wnt signaling in col mutants. The early dorsal and anterior patterning phenotypes of the col mutant embryos are selectively rescued by inactivation of Wnt8 function by morpholino translational interference. In contrast, the regionalized neuroectoderm posterioriorization phenotype is selectively rescued by morpholino-mediated inactivation of Wnt8b. These results suggest that col-mediated antagonism of early and late Wnt-signaling activity during gastrulation is normally required sequentially for both early dorsoventral patterning and the specification and patterning of regional fates within the anterior neuroectoderm.
脊椎动物身体模式的建立涉及外胚层、中胚层和内胚层沿背腹轴和前后轴的模式形成。来自几个多基因家族（包括Wnt）的众多信号分子之间的相互作用与调节这些过程有关。在这里，我们提供证据表明，斑马鱼colgate(b382)（col）突变导致Wnt信号增强，进而导致背侧和前部发育缺陷。col突变体在背腹模式形成方面表现出早期缺陷，表现为原肠胚形成期间背盾特异性标记物表达减少以及腹侧外侧表达基因的异位表达。除了这些早期模式形成缺陷外，col突变体在神经外胚层内还表现出显著的区域后化，导致前脑和中脑-后脑区域内前部命运减少而后部命运扩展。我们能够将这些表型与col突变体中Wnt信号的过度激活联系起来。通过吗啉代翻译干扰使Wnt8功能失活，可选择性地挽救col突变体胚胎的早期背侧和前部模式形成表型。相反，通过吗啉代介导的Wnt8b失活可选择性地挽救区域化的神经外胚层后化表型。这些结果表明，原肠胚形成期间col介导的早期和晚期Wnt信号活性拮抗作用通常是早期背腹模式形成以及前神经外胚层内区域命运的特化和模式形成所依次必需的。
