The graded response to Sonic Hedgehog depends on cilia architecture - PubMed (original) (raw)
The graded response to Sonic Hedgehog depends on cilia architecture
Tamara Caspary et al. Dev Cell. 2007 May.
Free article
Abstract
Several studies have linked cilia and Hedgehog signaling, but the precise roles of ciliary proteins in signal transduction remain enigmatic. Here we describe a mouse mutation, hennin (hnn), that causes coupled defects in cilia structure and Sonic hedgehog (Shh) signaling. The hnn mutant cilia are short with a specific defect in the structure of the ciliary axoneme, and the hnn neural tube shows a Shh-independent expansion of the domain of motor neuron progenitors. The hnn mutation is a null allele of Arl13b, a small GTPase of the Arf/Arl family, and the Arl13b protein is localized to cilia. Double mutant analysis indicates that Gli3 repressor activity is normal in hnn embryos, but Gli activators are constitutively active at low levels. Thus, normal structure of the ciliary axoneme is required for the cell to translate different levels of Shh ligand into differential regulation of the Gli transcription factors that implement Hedgehog signals.
Similar articles
- Cilia and Hedgehog responsiveness in the mouse.
Huangfu D, Anderson KV. Huangfu D, et al. Proc Natl Acad Sci U S A. 2005 Aug 9;102(32):11325-30. doi: 10.1073/pnas.0505328102. Epub 2005 Aug 1. Proc Natl Acad Sci U S A. 2005. PMID: 16061793 Free PMC article. - Defective ciliogenesis, embryonic lethality and severe impairment of the Sonic Hedgehog pathway caused by inactivation of the mouse complex A intraflagellar transport gene Ift122/Wdr10, partially overlapping with the DNA repair gene Med1/Mbd4.
Cortellino S, Wang C, Wang B, Bassi MR, Caretti E, Champeval D, Calmont A, Jarnik M, Burch J, Zaret KS, Larue L, Bellacosa A. Cortellino S, et al. Dev Biol. 2009 Jan 1;325(1):225-37. doi: 10.1016/j.ydbio.2008.10.020. Epub 2008 Oct 29. Dev Biol. 2009. PMID: 19000668 Free PMC article. - Primary cilia are critical for Sonic hedgehog-mediated dopaminergic neurogenesis in the embryonic midbrain.
Gazea M, Tasouri E, Tolve M, Bosch V, Kabanova A, Gojak C, Kurtulmus B, Novikov O, Spatz J, Pereira G, Hübner W, Brodski C, Tucker KL, Blaess S. Gazea M, et al. Dev Biol. 2016 Jan 1;409(1):55-71. doi: 10.1016/j.ydbio.2015.10.033. Epub 2015 Nov 2. Dev Biol. 2016. PMID: 26542012 Free PMC article. - The emergent design of the neural tube: prepattern, SHH morphogen and GLI code.
Ruiz i Altaba A, Nguyên V, Palma V. Ruiz i Altaba A, et al. Curr Opin Genet Dev. 2003 Oct;13(5):513-21. doi: 10.1016/j.gde.2003.08.005. Curr Opin Genet Dev. 2003. PMID: 14550418 Review. - Gli proteins in development and disease.
Hui CC, Angers S. Hui CC, et al. Annu Rev Cell Dev Biol. 2011;27:513-37. doi: 10.1146/annurev-cellbio-092910-154048. Epub 2011 Jul 21. Annu Rev Cell Dev Biol. 2011. PMID: 21801010 Review.
Cited by
- Mutations in mouse Ift144 model the craniofacial, limb and rib defects in skeletal ciliopathies.
Ashe A, Butterfield NC, Town L, Courtney AD, Cooper AN, Ferguson C, Barry R, Olsson F, Liem KF Jr, Parton RG, Wainwright BJ, Anderson KV, Whitelaw E, Wicking C. Ashe A, et al. Hum Mol Genet. 2012 Apr 15;21(8):1808-23. doi: 10.1093/hmg/ddr613. Epub 2012 Jan 6. Hum Mol Genet. 2012. PMID: 22228095 Free PMC article. - CCDC41 is required for ciliary vesicle docking to the mother centriole.
Joo K, Kim CG, Lee MS, Moon HY, Lee SH, Kim MJ, Kweon HS, Park WY, Kim CH, Gleeson JG, Kim J. Joo K, et al. Proc Natl Acad Sci U S A. 2013 Apr 9;110(15):5987-92. doi: 10.1073/pnas.1220927110. Epub 2013 Mar 25. Proc Natl Acad Sci U S A. 2013. PMID: 23530209 Free PMC article. - Intraciliary calcium oscillations initiate vertebrate left-right asymmetry.
Yuan S, Zhao L, Brueckner M, Sun Z. Yuan S, et al. Curr Biol. 2015 Mar 2;25(5):556-67. doi: 10.1016/j.cub.2014.12.051. Epub 2015 Feb 5. Curr Biol. 2015. PMID: 25660539 Free PMC article. - The serologically defined colon cancer antigen-3 (SDCCAG3) is involved in the regulation of ciliogenesis.
Yu F, Sharma S, Skowronek A, Erdmann KS. Yu F, et al. Sci Rep. 2016 Oct 21;6:35399. doi: 10.1038/srep35399. Sci Rep. 2016. PMID: 27767179 Free PMC article. - Arl13b Interacts With Vangl2 to Regulate Cilia and Photoreceptor Outer Segment Length in Zebrafish.
Song P, Dudinsky L, Fogerty J, Gaivin R, Perkins BD. Song P, et al. Invest Ophthalmol Vis Sci. 2016 Aug 1;57(10):4517-26. doi: 10.1167/iovs.16-19898. Invest Ophthalmol Vis Sci. 2016. PMID: 27571019 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Molecular Biology Databases