Park Maiyon, Moon Randall T
Howard Hughes Medical Institute, Department of Pharmacology and Center for Developmental Biology, University of Washington School of Medicine, Seattle, Washington 98195, USA.
Nat Cell Biol. 2002 Jan;4(1):20-5. doi: 10.1038/ncb716.
The gene strabismus (stbm)/Van Gogh (Vang) functions in the planar cell-polarity pathway in Drosophila. As the existence of such a pathway in vertebrates has not been firmly established, we investigated the functions and signalling activities encoded by stbm in vertebrate embryos. In regard to cell fate, inhibition of Stbm function in zebrafish embryos leads to reduction of anterior neural markers, whereas gain of function leads to a rise in the levels of these markers. In regard to cell behaviour, both gain-of-function and loss-of-function assays reveal a role for Stbm in mediating cell movements during gastrulation. Mechanistically, Stbm inhibits Wnt-mediated activation of beta-catenin-dependent transcription while promoting phosphorylation of c-Jun- and AP-1-dependent transcription. This complex effect on intracellular signalling pathways probably involves dishevelled (dsh), as Stbm was found to interact with the Dsh protein, and as Dsh is known to function in both planar cell-polarity and beta-catenin pathways in Drosophila.
斜视基因(stbm)/梵高基因(Vang)在果蝇的平面细胞极性通路中发挥作用。由于脊椎动物中尚未明确存在这样的通路,我们研究了stbm在脊椎动物胚胎中编码的功能和信号传导活性。在细胞命运方面,抑制斑马鱼胚胎中的Stbm功能会导致前神经标记物减少,而功能增强则会导致这些标记物水平升高。在细胞行为方面,功能获得和功能丧失实验均揭示了Stbm在原肠胚形成过程中介导细胞运动的作用。从机制上讲,Stbm抑制Wnt介导的β-连环蛋白依赖性转录激活,同时促进c-Jun和AP-1依赖性转录的磷酸化。这种对细胞内信号通路的复杂影响可能涉及蓬乱蛋白(dsh),因为发现Stbm与Dsh蛋白相互作用,并且已知Dsh在果蝇的平面细胞极性和β-连环蛋白通路中均发挥作用。