Dkk4 and Eda Regulate Distinctive Developmental Mechanisms for Subtypes of Mouse Hair

The mouse hair coat comprises protective “primary” and thermo-regulatory “secondary” hairs. Primary hair formation is ectodysplasin (Eda) dependent, but it has been puzzling that Tabby (Eda-/y) mice still make secondary hair. We report that Dickkopf 4 (Dkk4), a Wnt antagonist, affects an auxiliary pathway for Eda-independent development of secondary hair. A Dkk4 transgene in wild-type mice had no effect on primary hair, but secondary hairs were severely malformed. Dkk4 action on secondary hair was further demonstrated when the transgene was introduced into Tabby mice: the usual secondary follicle induction was completely blocked. The Dkk4-regulated secondary hair pathway, like the Eda-dependent primary hair pathway, is further mediated by selective activation of Shh. The results thus reveal two complex molecular pathways that distinctly regulate subtype-based morphogenesis of hair follicles, and provide a resolution for the longstanding puzzle of hair formation in Tabby mice lacking Eda

Identification of ectodysplasin-A receptor gene deletion at 2q12.2 and a potential autosomal MR locus

Mental retardation (MR) is not a common feature observed in patients with classical ectodermal dysplasias (EDs). Several genes responsible for EDs and MR have been identified. However, the causation has yet to be identified in a significant number of patients with either ED or MR. Here, we have molecularly characterized a de novo balanced translocation t(1;6)(p22.1;p22.1) in a female patient who had mild features of ED with hypodontia, microcephaly, and cognitive impairment. Mapping of the translocation breakpoints in the patient revealed no obvious causative gene for either ED or MR. Whole genome array CGH analysis unveiled two novel submicroscopic deletions at 2q12.2 and 6q22.3, unrelated to the translocation in the patient. The 2q12.2 deletion contains a known ED gene, ectodysplasin-A receptor (EDAR), and the loss of one copy of this gene is considered to be responsible for the ectodermal phenotype in the patient. It is plausible that a potential autosomal MR gene deleted at 2q12.2 or 6q22.3 is likely the cause of the neurodevelopmental defects in the patient