Glazer Andrew M, Wilkinson Alex W, Backer Chelsea B, Lapan Sylvain W, Gutzman Jennifer H, Cheeseman Iain M, Reddien Peter W
Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, MA 02142, USA.
Dev Biol. 2010 Jan 1;337(1):148-56. doi: 10.1016/j.ydbio.2009.10.025. Epub 2009 Oct 21.
Hedgehog signaling is critical for metazoan development and requires cilia for pathway activity. The gene iguana was discovered in zebrafish as required for Hedgehog signaling, and encodes a novel Zn finger protein. Planarians are flatworms with robust regenerative capacities and utilize epidermal cilia for locomotion. RNA interference of Smed-iguana in the planarian Schmidtea mediterranea caused cilia loss and failure to regenerate new cilia, but did not cause defects similar to those observed in hedgehog(RNAi) animals. Smed-iguana gene expression was also similar in pattern to the expression of multiple other ciliogenesis genes, but was not required for expression of these ciliogenesis genes. iguana-defective zebrafish had too few motile cilia in pronephric ducts and in Kupffer's vesicle. Kupffer's vesicle promotes left-right asymmetry and iguana mutant embryos had left-right asymmetry defects. Finally, human Iguana proteins (dZIP1 and dZIP1L) localize to the basal bodies of primary cilia and, together, are required for primary cilia formation. Our results indicate that a critical and broadly conserved function for Iguana is in ciliogenesis and that this function has come to be required for Hedgehog signaling in vertebrates.
刺猬信号通路对于后生动物的发育至关重要，且该信号通路的激活需要纤毛。在斑马鱼中发现了iguana基因，它是刺猬信号通路所必需的，编码一种新型锌指蛋白。涡虫是具有强大再生能力的扁虫，利用表皮纤毛进行运动。对地中海涡虫Schmidtea mediterranea中的Smed-iguana进行RNA干扰，会导致纤毛丧失且无法再生新的纤毛，但不会导致出现类似于刺猬信号通路RNA干扰动物中所观察到的缺陷。Smed-iguana基因的表达模式也与其他多个纤毛发生基因的表达模式相似，但这些纤毛发生基因的表达并不需要Smed-iguana。iguana缺陷型斑马鱼的前肾管和库普弗小泡中的活动纤毛过少。库普弗小泡促进左右不对称性，而iguana突变体胚胎存在左右不对称缺陷。最后，人类Iguana蛋白（dZIP1和dZIP1L）定位于初级纤毛的基体，并且二者共同参与初级纤毛的形成。我们的结果表明，Iguana的一个关键且广泛保守的功能是参与纤毛发生，并且在脊椎动物中，刺猬信号通路的激活也需要这一功能。
