Hedgehog-mediated patterning of the mammalian embryo requires transporter-like function of dispatched
Hedgehog-mediated patterning of the mammalian embryo requires transporter-like function of dispatched
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DOI：
10.1016/s0092-8674(02)00977-7
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发表时间：
2002-10-04
期刊：
影响因子：
64.5
通讯作者：
Beachy, PA
中科院分区：
文献类型：
--
作者：
Ma, Y;Erkner, A;Beachy, PA
disp基因是果蝇中Hedgehog（Hh）信号转导所必需的。在这里，我们证明了两个小鼠同源物，rnDispA，可以拯救果蝇disp功能，是必不可少的所有Hh图案活动在早期小鼠胚胎中检查。缺乏mDispA的胚胎成纤维细胞对外源性提供的Sonic hedgehog（Shh）信号正常应答，但在表达Shh时对其他应答细胞的刺激受损。我们已经开发了一种直接测量Disp蛋白在可溶性Hh蛋白释放中的活性的生化测定。该活性被Patched和细菌跨膜转运蛋白的相关家族中功能保守的残基的改变破坏，从而表明所有这些蛋白质的作用机制相似。
The dispatched (disp) gene is required for long-range Hedgehog (Hh) signaling in Drosophila. Here, we demonstrate that one of two murine homologs, rnDispA, can rescue disp function in Drosophila and is essential for all Hh patterning activities examined in the early mouse embryo. Embryonic fibroblasts lacking mDispA respond normally to exogenously provided Sonic hedgehog (Shh) signal, but are impaired in stimulation of other responding cells when expressing Shh. We have developed a biochemical assay that directly measures the activity of Disp proteins in release of soluble Hh proteins. This activity is disrupted by alteration of residues functionally conserved in Patched and in a related family of bacterial transmembrane transporters, thus suggesting similar mechanisms of action for all of these proteins.