The lanceolate hair rat phenotype results from a missense mutation in a calcium coordinating site of the desmoglein 4 gene.

Desmosomal cadherins are essential cell adhesion molecules present throughout the epidermis and other organs, whose major function is to provide mechanical integrity and stability to epithelial cells in a wide variety of tissues. We recently identified a novel desmoglein family member, Desmoglein 4 (Dsg4), using a positional cloning approach in two families with localized autosomal recessive hypotrichosis (LAH) and in the lanceolate hair (lah) mouse. In this study, we report cloning and identification of the rat Dsg4 gene, in which we discovered a missense mutation in a naturally occurring lanceolate hair (lah) rat mutant. Phenotypic analysis of lah/lah mutant rats revealed a striking hair shaft defect with the appearance of a lance head within defective hair shafts. The mutation disrupts a critical calcium binding site bridging the second and third extracellular domains of Dsg4, likely disrupting extracellular interactions of the protein.

Genes that are differentially expressed in rat vibrissa follicle germinative epithelium in vivo show altered expression patterns after extended organ culture.

Hair growth depends on maintenance of signalling between the dermal papilla and the germinative epithelium (GE), from which the differentiated layers of the hair fibre originate. Because no molecular studies have been reported which concentrate specifically on GE cells either in vivo or in vitro, we prepared a cDNA library enriched for messages which were highly expressed in GE cells to identify genes that may be involved in hair growth control. Of 35 subtracted library clones sequenced, 23 shared extensive homology with previously determined cDNA sequences, including LEF-1 and id4. Hair follicle organ culture models are often used to investigate the molecular basis of hair growth, although hair growth arrest occurs relatively rapidly in vitro. As an indicator of their role in follicle activities, we compared the expression of GE-specific clones in different regions of freshly isolated vibrissa follicles, with the corresponding regions of growth arrested, cultured follicles. Changes in the expression of some of these clones indicates that they could be related to fundamental cellular activities in the follicle. A library enriched for GE-specific clones therefore provides a useful source of candidate molecules for studies of follicular epithelial cell behaviour, both in vivo and in vitro.

Immunofluorescent localization of collagen types I, III, IV, fibronectin and laminin during morphogenesis of scales and scaleless skin in the chick embryo.

Collagen types I and III were purified from the skin of 3-or 7-week-old chickens, collagen type IV from bovine skin or EHS mouse tumour, fibronectin from human serum, and laminin from EHS mouse tumour. Antibodies were produced in rabbits or sheep, and used in indirect immunofluorescence on frozen sections of 9-to 16-day-old normal or mutant (scaleless) chick-embryo foot skin. In normal scale-forming skin and inscaleless skin, the distribution of anti-laminin and anti-type IV collagen label was uniform along the dermal-epidermal junction and showed no stage-related variations, except for fluorescent granules located in the dermis of early scale rudiments. By contrast, in normal scale-forming skin, the density of anti-types I and III label decreased in the dermis within scale rudiments, whereas it gradually increased in interscale skin. Conversely, anti-fibronectin label accumulated at a higher density within scale rudiments than in interscale skin. In the dermis of thescaleless mutant, anti-types I and III label and antifibronectin label were distributed evenly: the density of anti-collagen label increased with age, while that of antifibronectin decreased and almost completely vanished in 16-day-old skin, except around blood vessels. The microheterogeneous distribution of some extracellular matrix components, namely interstitial collagen types I and III and fibronectin, is interpreted as part of the morphogenetic message that the dermis is known to transmit to the epidermis during the formation of scales. The even distribution of these components in mutantscaleless skin is in agreement with this view. Basement membrane constituents laminin and type-IV collagen do not appear to be part of the dermal morphogenetic message.