title: The fickle finger of fate.
abstract: In this issue of the JCI, Niedermaier and colleagues demonstrate that a chromosomal inversion in mice results in dysregulation of Sonic hedgehog (Shh), such that Shh is ectopically expressed in a skeletogenic domain typically occupied by Indian hedgehog (Ihh). This molecular reversal eliminates phalangeal joint spaces, and consequently, Short digits (Dsh) heterozygotes (Dsh/+) have brachydactyly (shortened digits). Ihh is normally downregulated in regions that will become the joint space, but in Dsh/+ mice, Shh bypasses this regulatory control and persists; accordingly, cells maintain their chondrogenic fate and the developed digits are shorter than normal. The significance of these data extends far beyond the field of skeletal biology: they hint at the very real possibility that the endogenous Shh regulatory region contains a repressor designed to segregate the activity of Shh from Ihh. The existence of such a repressor provides a window into the distant past, revealing that Shh and Ihh must once have shared responsibilities in establishing tissue boundaries and orchestrating vertebrate tissue morphogenesis.
authors.affiliation: Department of Surgery, Stanford University, Stanford, California 94305, USA.
authors.forename: Luis
authors.initials: L
authors.lastname: de la Fuente
authors.forename: Jill A
authors.initials: JA
authors.lastname: Helms
mesh_terms: D000818:Animals; D007446:Chromosome Inversion; D005528:Foot / Q000033:anatomy & histology / Q000254:growth & development; D005532:Foot Deformities, Congenital; D018507:Gene Expression Regulation, Developmental; D053823:Hedgehog Proteins; D051379:Mice; D009024:Morphogenesis; D010012:Osteogenesis / Q000502:physiology; D010641:Phenotype; D015534:Trans-Activators / Q000235:genetics* / Q000378:metabolism
chemical_list: D053823:Hedgehog Proteins; C465570:Shh protein, mouse; D015534:Trans-Activators