The effect of pertussis toxin on zebrafish development: A possible role for inhibitory G-proteins in hedgehog signaling
The effect of pertussis toxin on zebrafish development: A possible role for inhibitory G-proteins in hedgehog signaling
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DOI：
10.1006/dbio.1997.8796
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发表时间：
1998-02-15
影响因子：
2.7
通讯作者：
McMahon, AP
中科院分区：
文献类型：
--
作者：
Hammerschmidt, M;McMahon, AP
最近的研究结果表明，cAMP依赖性蛋白激酶（PKA）作为一个负调节器的刺猬信号在脊椎动物胚胎的靶细胞。因此，PKA活性的抑制足以模拟接收Hedgehog信号的效果。我们已经探索了是否PKA抑制性Gi蛋白（GiPs）也可能参与Hedgehog信号的调节。将编码百日咳毒素（Ptx）的RNA注射到斑马鱼胚胎中，百日咳毒素是GiPs的特异性抑制剂。这些胚胎发育的表型性状与PKA调节亚基（dnPKA）的显性阴性形式的胚胎相反，包括眼睛的融合，前脑中缺乏腹侧规格，以及以牺牲后体节中的近轴命运为代价的硬结扩张。这些影响可以部分救出dnPKA的共表达，但不是由印度刺猬的共表达，这表明GIPs的PKA和刺猬下游的行为。其他刺猬和PKA依赖的过程，sclerotomal规范和近轴规范的前五个体节，没有负面影响Ptx。因此，GiPs可能参与一些但不是所有靶细胞中的Hedgehog信号传导。(C)北京：科学出版社.
Recent results have indicated that cAMP-dependent protein kinase (PKA) acts as a negative regulator of Hedgehog signaling in target cells of the vertebrate embryo. Consequently, suppression of PKA activity is sufficient to mimic the effect of receiving a Hedgehog signal. We have explored whether PKA-inhibiting Gi-proteins (GiPs) may also be involved in the regulation of Hedgehog signaling. Zebrafish embryos were injected with RNA encoding pertussis toxin (Ptx), a specific inhibitor of GiPs. These embryos developed phenotypic traits opposite to embryos expressing a dominant negative form of the PKA regulatory subunit (dnPKA), including a fusion of the eyes, a lack of ventral specification in the forebrain, and an expansion of the sclerotome at the expense of adaxial fates in the posterior somites. These effects can be partially rescued by coexpression of dnPKA, but not by coexpression of Indian Hedgehog, suggesting that GiPs act upstream of PKA and downstream of Hedgehogs. Other Hedgehog- and PKA-dependent processes, sclerotomal specification and adaxial specification in the first five somites, are not negatively affected by Ptx. Thus, GiPs may be involved in Hedgehog signaling in some, but not all target cells. (C) 1998 Academic Press.