Hsiung Frank, Ramirez-Weber Felipe-Andrès, Iwaki D David, Kornberg Thomas B
Department of Biochemistry and Biophysics, University of California, San Francisco, California 94143, USA.
Nature. 2005 Sep 22;437(7058):560-3. doi: 10.1038/nature03951.
The anterior/posterior (A/P) and dorsal/ventral (D/V) compartment borders that subdivide the wing imaginal discs of Drosophila third instar larvae are each associated with a developmental organizer. Decapentaplegic (Dpp), a member of the transforming growth factor-beta (TGF-beta) superfamily, embodies the activity of the A/P organizer. It is produced at the A/P organizer and distributes in a gradient of decreasing concentration to regulate target genes, functioning non-autonomously to regulate growth and patterning of both the anterior and posterior compartments. Wingless (Wg) is produced at the D/V organizer and embodies its activity. The mechanisms that distribute Dpp and Wg are not known, but proposed mechanisms include extracellular diffusion, successive transfers between neighbouring cells, vesicle-mediated movement, and direct transfer via cytonemes. Cytonemes are actin-based filopodial extensions that have been found to orient towards the A/P organizer from outlying cells. Here we show that in the wing disc, cytonemes orient towards both the A/P and D/V organizers, and that their presence and orientation correlates with Dpp signalling. We also show that the Dpp receptor, Thickveins (Tkv), is present in punctae that move along cytonemes. These observations are consistent with a role for cytonemes in signal transduction.
将果蝇三龄幼虫翅成虫盘划分为前后(A/P)和背腹(D/V)区室边界的每一个都与一个发育组织者相关联。转化生长因子-β(TGF-β)超家族成员之一的骨形态发生蛋白(Dpp)体现了A/P组织者的活性。它在A/P组织者处产生,并以浓度递减的梯度分布以调节靶基因,通过非自主作用来调节前后区室的生长和模式形成。无翅蛋白(Wg)在D/V组织者处产生并体现其活性。Dpp和Wg的分布机制尚不清楚,但提出的机制包括细胞外扩散、相邻细胞间的连续转移、囊泡介导的移动以及通过丝状伪足的直接转移。丝状伪足是基于肌动蛋白的丝状延伸物,已发现其从外围细胞朝向A/P组织者定向。在这里,我们表明在翅成虫盘中,丝状伪足同时朝向A/P和D/V组织者定向,并且它们的存在和定向与Dpp信号传导相关。我们还表明,Dpp受体厚脉(Tkv)存在于沿着丝状伪足移动的点状结构中。这些观察结果与丝状伪足在信号转导中的作用一致。