Fused has evolved divergent roles in vertebrate Hedgehog signalling and motile ciliogenesis
| Autor: | Catherine T. Nguyen, Miao-Hsueh Chen, Jehn Hsiahn Yang, Jie Huang, Jau-Nian Chen, Rhodora Gacayan, Pao-Tien Chuang, Christopher W. Wilson |
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| Rok vydání: | 2009 |
| Předmět: |
Genetics
Multidisciplinary Cilium Kinesins Biology biology.organism_classification Article Repressor Proteins Mice Transduction (genetics) Phenotype Axin Protein Ciliogenesis Animals Kinesin Hedgehog Proteins Cilia Signal transduction Microtubule-Associated Proteins Zebrafish Hedgehog Biogenesis Signal Transduction |
| Zdroj: | Nature. 459:98-102 |
| ISSN: | 1476-4687 0028-0836 |
| DOI: | 10.1038/nature07883 |
| Popis: | Hedgehog (Hh) signalling is essential for several aspects of embryogenesis. In Drosophila, Hh transduction is mediated by a cytoplasmic signalling complex that includes the putative serine-threonine kinase Fused (Fu) and the kinesin Costal 2 (Cos2, also known as Cos), yet Fu does not have a conserved role in Hh signalling in mammals. Mouse Fu (also known as Stk36) mutants are viable and seem to respond normally to Hh signalling. Here we show that mouse Fu is essential for construction of the central pair apparatus of motile, 9+2 cilia and offers a new model of human primary ciliary dyskinesia. We found that mouse Fu physically interacts with Kif27, a mammalian Cos2 orthologue, and linked Fu to known structural components of the central pair apparatus, providing evidence for the first regulatory component involved in central pair construction. We also demonstrated that zebrafish Fu is required both for Hh signalling and cilia biogenesis in Kupffer's vesicle. Mouse Fu rescued both Hh-dependent and -independent defects in zebrafish. Our results delineate a new pathway for central pair apparatus assembly, identify common regulators of Hh signalling and motile ciliogenesis, and provide insights into the evolution of the Hh cascade. |
| Databáze: | OpenAIRE |
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