9317397 Chuong Pattern formation is a crucial event in embryonic development. Identification of molecules and mechanisms involved in pattern formation have been the central interest of developmental biologists. Dr. Chuong is using feather morphogenesis as a model to study pattern formation and has focused on adhesion molecules and homeobox (Hox) genes. Dr. Chuong has shown that there are two kinds of Hox gradients in the integument: a "macro gradient" across the feather tract and a "micro gradient" across a single feather bud. The asynchronous alignment of different Hox macro gradient leads to a unique repertoire of position specific Hox expression patterns named Hox codes of skin appendages, which he hypothesizes determine the phenotype of skin appendages. Retinoic acid (RA) can transform feather phenotypes and alter the anterior-posterior axis of skin appendages, with concomitant changes in Hox expression. Epithelial-mesenchymal recombination revealed that the Hox micro gradient may be regulated by a signal from the epithelium. By the use of RA responsive element-LacZ- containing F9 cells it has been shown that a wave of endogenous RA activity propagates bilaterally from the midline. Dr. Chuong now suggests that 1) Hox codes of skin appendages determine the phenotype of skin appendages while the micro gradient determines the A-P axis of skin appendages, 2) The two gradients are regulated independently: the macro gradient may originate from the mesoderm, but the micro gradient is determined later and may be determined by the epithelium, and 3) RA is an endogenous morphogen in skin morphogenesis, with a dynamic distribution pattern during feather development similar to that of morphogenetic furrow in Drosophila eye development. To test these hypotheses, Dr. Chuong will ectopically express Hox genes on skin appendages in ovo using retroviral gene delivery. The ontogeny of Hox codes will be traced back to dermatome stage using DiI tracing and somite transpos ition. To search for the signals that regulate Hox gene expression, a model using epithelial-mesenchymal rotation/recombination of skin explants was developed in which the inducing signal can be analyzed. To test whether endogenous RA is involved in pattern formation, RARE-LacZ containing cell monolayers will be used to detect the dynamic RA distribution in developing skin. Aided by the distinct morphology of feathers, these novel approaches will add new dimensions to our understanding of pattern formation. ***
