The long term objective of the Chuong laboratory is to understand the molecular basis of pattern formation in embryonic development. Along this line, the PI has been using feather morphogenesis as a model and studying its molecular mechanisms. In this proposal, the PI will focus on signals involved in periodic patterning of feather primordia.
The formation of periodic patterns is fundamental in biology. Theoretical models describing these phenomena have been proposed for feather patterning. However, no molecular candidates have been identified. Based on results and preliminary data, the Chuong lab hypothesizes that the mechanism of periodic patterning in feathers has a global and a local component. 1 ) Local activators (candidates: FGFs, SHH) and inhibitors (candidates: BMPs) triggered from initial unstable small cell aggregates act in a reaction-diffusion mechanism to form individual primordia through competition for survival. 2) A global wave of competence (candidates: beta-catenin, signaling molecule receptors) propagating from one end of the primary row, imposing additional activator activities, thus organizing competent cells in the tract field progressively and effectively into a functional feather tract.
The general approach is to map and analyze, with in situ hybridization and immunochemical localization, the expression sequences and modes of candidate molecules in normal and experimental conditions. Signaling molecules coated on beads and candidate genes and their mutated forms carried in retroviral vectors will be used to perturb feather formation.
Induction is the key event in organ formation. Many researchers have focused on the pursuit of the inducer. Previously, the PI showed that SHH is one of the earliest molecules in feather initiation, but what molecules are upstream of SHH? If it is X, what is upstream of X? This type of pursuit will have no ending. Somewhere, there should be a forming process resulted from intrinsic cell properties, rather than from a specific molecular marker. This proposal represents a new approach to answer the fundamental "induction" question. The Chuong lab will test alternative ideas, molecules and to revise the hypotheses depending on the results obtained from the laboratory and the field. The works will contribute to the understanding of the cellular and molecular mechanisms of organogenesis in general.
