Composition and dosage of a multipartite enhancer cluster control developmental expression of Ihh (Indian hedgehog)

Stefan Mundlos, Dario Lupianez and colleagues investigate CNVs involving the regulatory landscape of IHH (Indian hedgehog), which cause craniosynostosis and synpolydactyly. Using genetic manipulation in mice, they show that Ihh is regulated by at least nine enhancers with individual tissue specificities and that duplications in this region can cause dose-dependent upregulation and also misexpression of Ihh.