PUBLICATION

Fused has evolved divergent roles in vertebrate Hedgehog signalling and motile ciliogenesis

Authors
Wilson, C.W., Nguyen, C.T., Chen, M.H., Yang, J.H., Gacayan, R., Huang, J., Chen, J.N., and Chuang, P.T.
ID
ZDB-PUB-090324-16
Date
2009
Source
Nature   459(7243): 98-102 (Journal)
Registered Authors
Chen, Jau-Nian, Huang, Jie, Nguyen, Catherine
Keywords
none
MeSH Terms
  • Animals
  • Axin Protein
  • Cilia/physiology*
  • Hedgehog Proteins/physiology*
  • Kinesins/metabolism
  • Mice
  • Microtubule-Associated Proteins/metabolism
  • Phenotype
  • Repressor Proteins/genetics
  • Repressor Proteins/metabolism*
  • Signal Transduction/physiology*
  • Zebrafish/embryology
PubMed
19305393 Full text @ Nature
Abstract
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.
Genes / Markers
Figures
Show all Figures
Expression
Phenotype
Mutation and Transgenics
Human Disease / Model Data
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping
Errata and Notes