Jang Anna C-C, Chang Yu-Chiuan, Bai Jianwu, Montell Denise
Department of Biological Chemistry, Johns Hopkins School of Medicine, 725 North Wolfe Street, Baltimore, Maryland 21205-2185, USA.
Nat Cell Biol. 2009 May;11(5):569-79. doi: 10.1038/ncb1863. Epub 2009 Apr 6.
During development, elaborate patterns of cell differentiation and movement must occur in the correct locations and at the proper times. Developmental timing has been studied less than spatial pattern formation, and the mechanisms integrating the two are poorly understood. Border-cell migration in the Drosophila ovary occurs specifically at stage 9. Timing of the migration is regulated by the steroid hormone ecdysone, whereas spatial patterning of the migratory population requires localized activity of the JAK-STAT pathway. Ecdysone signalling is patterned spatially as well as temporally, although the mechanisms are not well understood. In stage 9 egg chambers, ecdysone signalling is highest in anterior follicle cells including the border cells. We identify the gene abrupt as a repressor of ecdysone signalling and border-cell migration. Abrupt protein is normally lost from border-cell nuclei during stage 9, in response to JAK-STAT activity. This contributes to the spatial pattern of the ecdysone response. Abrupt attenuates ecdysone signalling by means of a direct interaction with the basic helix-loop-helix (bHLH) domain of the P160 ecdysone receptor coactivator Taiman (Tai). Taken together, these findings provide a molecular mechanism by which spatial and temporal cues are integrated.
在发育过程中,细胞分化和运动的精细模式必须在正确的位置和适当的时间发生。与空间模式形成相比,发育时间的研究较少,而且整合两者的机制也知之甚少。果蝇卵巢中的边缘细胞迁移特定发生在第9阶段。迁移的时间由类固醇激素蜕皮激素调节,而迁移群体的空间模式形成则需要JAK-STAT信号通路的局部活性。尽管其机制尚不清楚,但蜕皮激素信号在空间和时间上都呈模式化。在第9阶段的卵室中,蜕皮激素信号在前部卵泡细胞(包括边缘细胞)中最高。我们鉴定出基因abrupt是蜕皮激素信号和边缘细胞迁移的抑制因子。在第9阶段,响应JAK-STAT活性,边缘细胞核中的Abrupt蛋白通常会消失。这有助于蜕皮激素反应的空间模式形成。Abrupt通过与P160蜕皮激素受体共激活因子Taiman(Tai)的基本螺旋-环-螺旋(bHLH)结构域直接相互作用来减弱蜕皮激素信号。综上所述,这些发现提供了一种整合空间和时间线索的分子机制。