Generating and Interpreting a Developmental Gradient in the Drosophila Wing

University Of Pittsburgh, Pittsburgh PA

Investigators

Abstract

Generating and interpreting a developmental gradient in the Drosophila wing Gerard L. Campbell Secreted signaling proteins such as Wnts and BMPs, control cell differentiation during embryogenesis in animals by regulating gene expression. These proteins are often distributed as extracellular gradients surrounding cells secreting them; in responding cells, they modulate the activity or expression of specific transcription factors (TFs), which, in turn, show graded distribution. These TF gradients can generate patterns of cell differentiation if the TF can regulate different target genes above distinct threshold concentrations: for example, some differentiation-specific genes may be activated only by high levels of the TF and will be expressed close to the source of the signaling protein, while others may be activated by lower levels and will be expressed further away. This project will investigate how a gradient of one TF, Brinker (Brk), is established in the developing wing of the fruit fly, Drosophila and determine why some genes are high-response targets while others are low-response. The Brk gradient is established by an extracellular gradient of Dpp, a BMP; the mechanisms involved will be analyzed, including negative feedback by Brk itself and how BMP signaling impacts the brk regulatory region. The omb and sal genes are high and low-response Brk targets, respectively; the regulatory elements of these genes will be dissected to uncover the molecular basis of this differential sensitivity. Intellectual merit of the proposed activity Our understanding of embryogenesis has made remarkable progress in recent years, and the importance of TF gradients in this process has been demonstrated most elegantly in the Drosophila embryo. However, outside of this system there is a remarkable lack of relevant studies so that the Drosophila wing provides an excellent system to extend our understanding. These studies will shed light on how similar gradients control patterning in other organisms, including mammals and humans, possibly providing insights into specific diseases, particularly congenital birth defects that may result from a failure to generate appropriate gradients. Broader Impacts resulting from the proposed activity The University of Pittsburgh has a diverse student body and this proposal will provide one graduate student and several undergraduate students with the opportunity to engage in research in a premier undergraduate biological sciences department. The PI teaches an undergraduate developmental biology laboratory course which exposes students to Drosophila and the techniques used here; it also allows them to conduct experiments similar to those published and proposed here