ADHESION MOLECULES AND HOMEOPROTEINS IN THE PHENOTYPIC DETERMINATION OF SKIN APPENDAGES

We examined the roles of adhesion molecules and homeoproteins in the m orphogenesis of skin appendages using feather as a model. The expressi on pattern of these molecules in different stages of feather developme nt were very dynamic. For example, neural cell adhesion molecules are present first in the dermal condensations, then in distal bud epitheli um, then in the dermal papilla, and finally in the marginal and axial plates. Tenascin is present first in the placode, then in the anterior bud epithelium and mesoderm, and then in the dermal papilla. The expr ession patterns suggest that the adhesion molecules are involved in fo rming the boundary of cell groups that interact to form skin appendage s. Antibody perturbation of embryonic skin-explant cultures showed tha t liver cell adhesion molecules are involved in establishing the hexag onal pattern, neural cell adhesion molecules are involved in the forma tion of dermal condensations, tenascin appears to be involved in the g rowth of feather buds, and integrin is essential for epithelial-mesenc hymal interactions. Using antibodies to XlHbox 1 (similar to Hox 3.3 o r C6) and Hox 4.2 (or D4), we showed that there is a homeoprotein grad ient within the feather buds, and that the expression pattern is posit ion-specific. It is hypothesized that Hox codes, derived from the comb ined expression pattern of homeoproteins, determine the phenotypes and orientation of skin appendages. Experiments using retinoids in the me dia or retinoid-soaked beads to create a local retinoid gradient are c onsistent with this hypothesis. As demonstrated here, feather developm ent provides an excellent opportunity to analyze the molecular cascade of skin-appendage morphogenesis.