J Inv Der-Liu-comment Widelitz

See related article on page 264RegulatingtheRegulators:RoutingtheWnt-b-Catenin–LefSignalsRandall B. WidelitzDepartment of Pathology, University of Southern California, Keck School of Medicine, Los Angeles, CaliforniaAs genomic sequences are identified, the next frontier to- staining the mesenchyme (E11) and epithelium (by E12) ofward effective genetic medicine will be to identify how gene wild-type mouse vibrissae. Constant expression in the me-expressionisregulated,soectopicgenescanbeexpressed senchyme but transient expression of Lef-1 in the epithe-in appropriate locations, at appropriate times and to ap- lium is required for normal whisker formation. Lef-1 knock-propriate therapeutic levels. This is especially true for mol- out mice lack hairs, teeth, mammary glands, and other ep-ecules that regulate the downstream expression of a ithelial-derived skin appendages (van Genderen et al, 1994).cascade of genes. Like traffic control regulators, these Mice expressing an NH -terminal truncation of Lef-1 in the2molecules effectively act as molecular switches, which can skin epidermis form interfollicular skin rather than hairs orfavor one pathway or another with dramatic biological con- formsebaceoustumors(Niemannetal,2002).b-Catenin andsequences. For years scientists have tried to map the Lef-1 form a complex to suppress E-cadherin expressiontranscriptional regulatory regions of structural effector presumably while inducing the expression of other genesmolecules ...