Han Chun, Belenkaya Tatyana Y, Wang Bei, Lin Xinhua
Division of Developmental Biology, Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
Development. 2004 Feb;131(3):601-11. doi: 10.1242/dev.00958. Epub 2004 Jan 7.
The signalling molecule Hedgehog (Hh) functions as a morphogen to pattern a field of cells in animal development. Previous studies in Drosophila have demonstrated that Tout-velu (Ttv), a heparan sulphate polymerase, is required for Hh movement across receiving cells. However, the molecular mechanism of Ttv- mediated Hh movement is poorly defined. We show that Dally and Dally-like (Dly), two Drosophila glypican members of the heparan sulphate proteoglycan (HSPG) family, are the substrates of Ttv and are essential for Hh movement. We show that embryos lacking dly activity exhibit defects in Hh distribution and its subsequent signalling. However, both Dally and Dly are involved and are functionally redundant in Hh movement during wing development. We further demonstrate that Hh movement in its receiving cells is regulated by a cell-to-cell mechanism that is independent of dynamin-mediated endocytosis. We propose that glypicans transfer Hh along the cell membrane to pattern a field of cells.
信号分子刺猬索尼克（Hh）在动物发育过程中作为一种形态发生素，为细胞区域提供模式。先前在果蝇中的研究表明，硫酸乙酰肝素聚合酶Tout-velu（Ttv）是Hh穿过接收细胞所必需的。然而，Ttv介导的Hh移动的分子机制尚不清楚。我们发现，硫酸乙酰肝素蛋白聚糖（HSPG）家族的两个果蝇磷脂酰肌醇蛋白聚糖成员Dally和类Dally（Dly）是Ttv的底物，并且对Hh移动至关重要。我们发现，缺乏dly活性的胚胎在Hh分布及其后续信号传导方面存在缺陷。然而，在翅发育过程中，Dally和Dly都参与了Hh移动，并且在功能上是冗余的。我们进一步证明，Hh在其接收细胞中的移动受一种细胞间机制调节，该机制独立于发动蛋白介导的内吞作用。我们提出，磷脂酰肌醇蛋白聚糖沿着细胞膜转移Hh，从而为细胞区域提供模式。
