Hedgehog signalling in the mouse requires intraflagellar transport proteins
Hedgehog signalling in the mouse requires intraflagellar transport proteins
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DOI：
10.1038/nature02061
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发表时间：
2003-11-06
期刊：
影响因子：
64.8
通讯作者：
Anderson, KV
中科院分区：
文献类型：
--
作者：
Huangfu, DW;Liu, AM;Anderson, KV
鞭毛内转运（IFT）蛋白首次被鉴定为单细胞莱茵衣藻鞭毛生长和维持的必需因子（1）。在筛选胚胎图案化突变诱导的乙基亚硝基脲，在这里，我们确定了两个小鼠突变体，wimple（wim）和flexo（fxo），缺乏腹神经细胞类型，并显示其他表型特征的缺陷，在音速刺猬信号。这两种突变都破坏了IFT蛋白：wim突变是先前未表征的小鼠IFFT 172同源物的等位基因; fxo是polaris的新亚型等位基因，polaris是小鼠IFFT 88同源物。遗传分析表明，Wim，Polaris和IFT马达蛋白Kif 3a是刺猬信号传导所需的，位于Patched 1（刺猬受体）下游和刺猬信号传导直接靶点上游。我们的数据表明，IFT机制在刺猬信号转导中具有重要的和脊椎动物特异性的作用。
Intraflagellar transport (IFT) proteins were first identified as essential factors for the growth and maintenance of flagella in the single-celled alga Chlamydomonas reinhardtii(1). In a screen for embryonic patterning mutations induced by ethylnitrosourea, here we identify two mouse mutants, wimple (wim) and flexo (fxo), that lack ventral neural cell types and show other phenotypes characteristic of defects in Sonic hedgehog signalling. Both mutations disrupt IFT proteins: the wim mutation is an allele of the previously uncharacterized mouse homologue of IFT172; and fxo is a new hypomorphic allele of polaris, the mouse homologue of IFT88. Genetic analysis shows that Wim, Polaris and the IFT motor protein Kif3a are required for Hedgehog signalling at a step downstream of Patched1 ( the Hedgehog receptor) and upstream of direct targets of Hedgehog signalling. Our data show that IFT machinery has an essential and vertebrate-specific role in Hedgehog signal transduction.