Drosophila embryogenesis is characterized by a highly orchestrated set of events directed by a regulatory gene cascade that creates a coordinate system along the anterior-posterior and dorsal-ventral axes of the embryo. This process must be highly canalized to suppress developmental noise introduced by environmental and mutational variation. But prior to cellularization, the steps in creating morphogenetic landmarks are diffusion mediated and are expected to be sensitive to initial morphogen concentrations, egg morphology, and environmental conditions (such as temperature). These factors vary extensively within and between species. The general aim of the proposal is to investigate the extent and mechanisms by which genetic and environmental variation is suppressed during patterning of the anterior-posterior axis in Drosophila development, and how these canalizing mechanisms respond to evolutionary changes in the coordinate system between species. Experiments will be carried out to: Test the hypothesis that ds-regulatory elements are building blocks of canalization Measure the sensitivity of the anterior-posterior patterning pathway to modulation of expression levels and positioning of its constituent genes Investigate genetic variation in pattern formation among isogenic strains differing in egg size and in development rate. Compare closely related species of Drosophila for the same traits to investigate the evolution of canalization of anterior-posterior patterning. Similar mechanisms to suppress environmental and genetic variation are expected to be acting in human development. The proposed research may lead to a better understanding of concealed gene polymorphism in humans, which when expressed may contribute to individual variation in disease susceptibility or resistance, drug response and side effects, as well as other medically relevant traits. ? ? ?
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