Cytonemes are required for the establishment of a normal Hedgehog morphogen gradient in Drosophila epithelia.
Cytonemes are required for the establishment of a normal Hedgehog morphogen gradient in Drosophila epithelia.
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DOI：
10.1038/ncb2856
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发表时间：
2013-11
影响因子：
21.3
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中科院分区：
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Hedgehog（Hh）信号传导在发育、干细胞生物学和疾病中是重要的。在多种组织中，Hh作为形态发生素调节生长和细胞命运特化。已经提出了几种假说来解释形态发生体的运动，其中之一是通过称为细胞丝的丝状伪足样突起进行运输。在这里，我们分析的机制Hh运动在果蝇的翅盘和腹部表皮。我们发现，在这两个上皮细胞，细胞产生的Hh信号的区域中的cytonemes。这些突起是基于肌动蛋白的，跨越几个细胞直径。各种Hh信号成分定位于细胞丝，以及点状结构，移动沿着细胞丝，可能是外囊泡。使用在体内成像，我们表明，cytonemes是动态的结构和Hh梯度的建立与cytonemes的形成在空间和时间。事实上，影响细胞丝形成的突变体条件降低了细胞丝长度和Hh梯度长度。我们的研究结果表明，细胞丝介导的Hh运输是Hh梯度形成的机制基础。
Hedgehog (Hh) signalling is important in development, stem cell biology and disease. In a variety of tissues, Hh acts as a morphogen to regulate growth and cell fate specification. Several hypotheses have been proposed to explain morphogen movement, one of which is transport via filopodia-like protrusions called cytonemes. Here, we analyse the mechanism underlying Hh movement in the wing disc and the abdominal epidermis of Drosophila. We show that, in both epithelia, cells generate cytonemes in regions of Hh signalling. These protrusions are actin-based and span several cell diameters. Various Hh signalling components localise to cytonemes, as well as to punctate structures that move along cytonemes and are probably exovesicles. Using in vivo imaging, we show that cytonemes are dynamic structures and that Hh gradient establishment correlates with cytoneme formation in space and time. Indeed, mutant conditions that affect cytoneme formation reduce both cytoneme length and Hh gradient length. Our results suggest that cytoneme-mediated Hh transport is the mechanistic basis for Hh gradient formation.