Evc is a positive mediator of Ihh-regulated bone growth that localises at the base of chondrocyte cilia
- PMID: 17660199
- DOI: 10.1242/dev.007542
Evc is a positive mediator of Ihh-regulated bone growth that localises at the base of chondrocyte cilia
Abstract
EVC is a novel protein mutated in the human chondroectodermal dysplasia Ellis-van Creveld syndrome (EvC; OMIM: 225500). We have inactivated Evc in the mouse and show that Evc(-/-) mice develop an EvC-like syndrome, including short ribs, short limbs and dental abnormalities. lacZ driven by the Evc promoter revealed that Evc is expressed in the developing bones and the orofacial region. Antibodies developed against Evc locate the protein at the base of the primary cilium. The growth plate of Evc(-/-) mice shows delayed bone collar formation and advanced maturation of chondrocytes. Indian hedgehog (Ihh) is expressed normally in the growth plates of Evc(-/-) mice, but expression of the Ihh downstream genes Ptch1 and Gli1 was markedly decreased. Recent studies have shown that Smo localises to primary cilia and that Gli3 processing is defective in intraflagellar transport mutants. In vitro studies using Evc(-/-) cells demonstrate that the defect lies downstream of Smo. Chondrocyte cilia are present in Evc(-/-) mice and Gli3 processing appears normal by western blot analysis. We conclude that Evc is an intracellular component of the hedgehog signal transduction pathway that is required for normal transcriptional activation of Ihh target genes.
Similar articles
-
The ciliary Evc/Evc2 complex interacts with Smo and controls Hedgehog pathway activity in chondrocytes by regulating Sufu/Gli3 dissociation and Gli3 trafficking in primary cilia.Hum Mol Genet. 2013 Jan 1;22(1):124-39. doi: 10.1093/hmg/dds409. Epub 2012 Oct 1. Hum Mol Genet. 2013. PMID: 23026747
-
Evc works in chondrocytes and osteoblasts to regulate multiple aspects of growth plate development in the appendicular skeleton and cranial base.Bone. 2012 Jan;50(1):28-41. doi: 10.1016/j.bone.2011.08.025. Epub 2011 Aug 31. Bone. 2012. PMID: 21911092
-
The hedgehog target Vlk genetically interacts with Gli3 to regulate chondrocyte differentiation during mouse long bone development.Differentiation. 2013 Apr-Jun;85(4-5):121-30. doi: 10.1016/j.diff.2013.03.002. Epub 2013 Jun 19. Differentiation. 2013. PMID: 23792766
-
Ellis-van Creveld syndrome and Weyers acrodental dysostosis are caused by cilia-mediated diminished response to hedgehog ligands.Am J Med Genet C Semin Med Genet. 2009 Nov 15;151C(4):341-51. doi: 10.1002/ajmg.c.30226. Am J Med Genet C Semin Med Genet. 2009. PMID: 19876929 Review.
-
Role of primary cilia and Hedgehog signaling in craniofacial features of Ellis-van Creveld syndrome.Am J Med Genet C Semin Med Genet. 2022 Mar;190(1):36-46. doi: 10.1002/ajmg.c.31969. Epub 2022 Apr 8. Am J Med Genet C Semin Med Genet. 2022. PMID: 35393766 Review.
Cited by
-
Specific variants in WDR35 cause a distinctive form of Ellis-van Creveld syndrome by disrupting the recruitment of the EvC complex and SMO into the cilium.Hum Mol Genet. 2015 Jul 15;24(14):4126-37. doi: 10.1093/hmg/ddv152. Epub 2015 Apr 23. Hum Mol Genet. 2015. PMID: 25908617 Free PMC article.
-
The deubiquitinating enzyme Usp14 controls ciliogenesis and Hedgehog signaling.Hum Mol Genet. 2019 Mar 1;28(5):764-777. doi: 10.1093/hmg/ddy380. Hum Mol Genet. 2019. PMID: 30388222 Free PMC article.
-
Genome wide association and gene enrichment analysis reveal membrane anchoring and structural proteins associated with meat quality in beef.BMC Genomics. 2019 Feb 21;20(1):151. doi: 10.1186/s12864-019-5518-3. BMC Genomics. 2019. PMID: 30791866 Free PMC article.
-
Phenotypic Variation in Patients with Homozygous c.1678G>T Mutation in EVC Gene: Report of Two Mexican Families with Ellis-van Creveld Syndrome.Am J Case Rep. 2017 Dec 12;18:1325-1329. doi: 10.12659/ajcr.905976. Am J Case Rep. 2017. PMID: 29229899 Free PMC article.
-
Hedgehog signaling mechanism and role in cancer.Semin Cancer Biol. 2022 Oct;85:107-122. doi: 10.1016/j.semcancer.2021.04.003. Epub 2021 Apr 6. Semin Cancer Biol. 2022. PMID: 33836254 Free PMC article. Review.
Publication types
MeSH terms
Substances
Grants and funding
LinkOut - more resources
Full Text Sources
Medical
Molecular Biology Databases
Miscellaneous
