Pattern Formation in the Wing of Drosophila

University Of Wisconsin-Madison, Madison WI

Investigators

Abstract

Project Summary- Pattern formation in the wing of Drosophila (S.S. Blair, PI) 1) Intellectual Merit- The normal development of embryos requires the precise specification of specific tissue types, and failures in that specification underlie many birth defects and congenital diseases. Signaling between tissues and cells during development often plays a critical role in this process. However, the details underlying many important signaling pathways and how those signals are transmitted in developing tissues is still quite poorly understood. This project examines the way in which important signals, mediated by the BMP class of TGFbs, are transmitted over long distance, and how that signaling is modified by extracellular proteins. The model system used for this work is the wing of the fruitfly, Drosophila melanogaster. The advantages of this model system are several: the genetic and molecular analyses possible in Drosophila are perhaps unmatched by any other animal, and the mechanisms underlying development of the Drosophila wing shows several striking parallels with the mechanisms used in humans and other mammals. The work focuses specifically on the development of the crossveins within the wing, and the role played by two BMP-like signaling molecules (Decapentaplegic and Glass bottom boat), three proteins that bind BMPs, (Short gastrulation, Twisted gastrulation-2, Crossveinless 2), and the protease Tolkin, which can regulate the activity of Short gastrulation by cleaving it. The evidence outlined in the proposal indicates that the crossveins, unlike the other veins, require BMP formation for their initial development. Moreover, the crossveins are exquisitely sensitive to an unusual aspect of BMP signaling: the stimulation of long-distance signaling by BMP-binding molecules. These molecules are best known for their ability to act as inhibitors of signaling by sequestering BMPs from their receptors. Nonetheless, preliminary data shows that the BMP-binding molecules are required for signaling in the crossveins. Aim 1 examines the way in which these molecule act, examining in detail where they are required, which ligand they act upon, and how they affect BMP diffusion. Aim 2 examines the Crossveinless 2 protein, testing theories that it acts on Short gastrulation function in vivo and in vitro. Aim 3 characterizes novel genetic loci that affect crossvein development. 2) Broader impact. The research funded will be of obvious relevance to those working on developmental biology of vertebrates and invertebrates. This research also helps train both graduate students and undergraduates. The PI's lab usually supports 4-5 graduate students and 2-3 undergraduates per year, and these carry out the brunt of the research. The latter are involved not only in independent study classes, but also rotate through the PI's lab as part of the introductory biology sequence at the University of Wisconsin-Madison. Many of these students have gone on to productive careers in the biosciences, as graduate students, postdocs or faculty. The PI is also heavily involved in undergraduate education, and this teaching is heavily informed by the PI's research program. The PI has also been very involved in writing reviews for the field and in turn as acting as a referee for manuscripts and grants. The PI maintains a web site detailing techniques for immunohistological and mosaic techniques in Drosophila as a guide for those new to the field (http://bender.zoology.wisc.edu/antiweb.html).