Cho Seo-Hee, Cepko Constance L
Department of Genetics and Howard Hughes Medical Institute, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, MA 02115, USA.
Development. 2006 Aug;133(16):3167-77. doi: 10.1242/dev.02474. Epub 2006 Jul 19.
Wnt signaling orchestrates multiple aspects of central nervous system development, including cell proliferation and cell fate choices. In this study, we used gene transfer to activate or inhibit canonical Wnt signaling in vivo in the developing eye. We found that the expression of Wnt2b or constitutively active (CA) beta-catenin inhibited retinal progenitor gene (RPG) expression and the differentiation of retinal neurons. In addition, Wnt signal activation in the central retina was sufficient to induce the expression of markers of the ciliary body and iris, two tissues derived from the peripheral optic cup (OC). The expression of a dominant-negative (DN) allele of Lef1, or of a Lef1-engrailed fusion protein, led to the inhibition of expression of peripheral genes and iris hypoplasia, suggesting that canonical Wnt signaling is required for peripheral eye development. We propose that canonical Wnt signaling in the developing optic vesicle (OV) and OC plays a crucial role in determining the identity of the ciliary body and iris. Because wingless (wg) plays a similar role in the induction of peripheral eye tissues of Drosophila, these findings indicate a possible conservation of the process that patterns the photoreceptive and support structures of the eye.
Wnt信号通路调控中枢神经系统发育的多个方面,包括细胞增殖和细胞命运选择。在本研究中,我们利用基因转移在发育中的眼睛中体内激活或抑制经典Wnt信号通路。我们发现,Wnt2b或组成型激活(CA)的β-连环蛋白的表达抑制视网膜祖细胞基因(RPG)的表达以及视网膜神经元的分化。此外,中央视网膜中的Wnt信号激活足以诱导睫状体和虹膜标志物的表达,这两种组织源自周边视杯(OC)。Lef1的显性负性(DN)等位基因或Lef1-engrailed融合蛋白的表达导致周边基因表达的抑制和虹膜发育不全,表明经典Wnt信号通路是周边眼发育所必需的。我们提出,发育中的视泡(OV)和OC中的经典Wnt信号通路在确定睫状体和虹膜的特性中起关键作用。由于无翅(wg)在果蝇周边眼组织的诱导中起类似作用,这些发现表明在构建眼睛的感光和支持结构的过程中可能存在保守性。