Jopling Chris, Hertog Jeroen den
Hubrecht Laboratory, Netherlands Institute for Developmental Biology, Uppsalalaan 8, 3584 CT Utrecht, The Netherlands.
Mech Dev. 2007 Feb;124(2):129-36. doi: 10.1016/j.mod.2006.10.003. Epub 2006 Oct 28.
Morphogenetic cell movements during gastrulation shape the vertebrate embryo bodyplan. Non-canonical Wnt signaling has been established to regulate convergence and extension cell movements that mediate anterior-posterior axis elongation. In recent years, many other factors have been implicated in the process by modulation of non-canonical Wnt signaling or by different, unknown mechanisms. We have found that the Src family kinases, Fyn and Yes, are required for normal convergence and extension cell movements in zebrafish embryonic development and they signal in parallel to non-canonical Wnts, eventually converging on a common downstream factor, RhoA. Here, we report that Csk, a negative regulator of Src family kinases has a role in gastrulation cell movements as well. Csk knock down induced a phenotype that was similar to the defects observed after knock down of Fyn and Yes, in that gastrulation cell movements were impaired, without affecting cell fate. The Csk knock down phenotype was rescued by simultaneous partial knock down of Fyn and Yes. We conclude that Csk acts upstream of Fyn and Yes to control vertebrate gastrulation cell movements.
原肠胚形成过程中的形态发生细胞运动塑造了脊椎动物胚胎的身体结构。非经典Wnt信号通路已被证实可调节介导前后轴伸长的汇聚和延伸细胞运动。近年来,许多其他因素通过调节非经典Wnt信号通路或通过不同的未知机制参与了这一过程。我们发现,Src家族激酶Fyn和Yes是斑马鱼胚胎发育中正常汇聚和延伸细胞运动所必需的,它们与非经典Wnt信号平行发挥作用,最终汇聚于一个共同的下游因子RhoA。在此,我们报告Src家族激酶的负调控因子Csk在原肠胚形成细胞运动中也发挥作用。敲低Csk会诱导出一种与敲低Fyn和Yes后观察到的缺陷相似的表型,即原肠胚形成细胞运动受损,但不影响细胞命运。同时部分敲低Fyn和Yes可挽救Csk敲低表型。我们得出结论,Csk在Fyn和Yes的上游发挥作用,以控制脊椎动物原肠胚形成细胞运动。