An important problem in developmental biology is how positional information created by threshold responses to diffusible signals is translated into the formation of specialized morphological structures at different locations. The initiation of wing vein development in Drosophila provides a particularly favorable system for investigating this link between patterning and formation of adult structures. A great deal is already known about how positions are specified along the primary axes of the wing and how this information leads to initiation of vein-specific patterns of gene expression in different vein primordia. The overall goal of this grant proposal is to understand the mechanism by which positional information is converted into vein specific differentiation programs for the second and fifth longitudinal wing veins, which form at opposite positions along the anterior-posterior axis of the wing. Previous analysis revealed that veins form in narrow lines along boundaries between abutting domains of cells. Vein primordia form along the edge of one domain of cells in response to diffusible short range signals emanating from adjacent cells that are unable to respond to the vein inducing signal they produce. A central aim in understanding this """"""""for-export-only"""""""" mode of signaling is to determine the molecular identity of the putative vein inductive signals. In addition to analyzing the mechanisms by which vein morphogenesis is initiated, we will also compare the activities of the knirps(kni) and abrupt (ab) genes, which play key roles in organizing vein specific gene expression programs in the second and fifth vein primordia respectively. The proposed experiments are relevant to human health in two ways. First, the problem of forming lines during development is a general process. Consequently, insights gained from the proposed experiments will be applicable to many vertebrate stages of development. Second, defects in several genes involved in determining the positions of veins cause birth defects or cancer when mutated in humans. Thus, knowledge gained from these studies should have broad applications to understanding vertebrate development as well as offering possible insights into mechanisms of human disease.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM060585-07
Application #
6990539
Study Section
Cell Development and Function Integrated Review Group (CDF)
Program Officer
Haynes, Susan R
Project Start
2000-01-01
Project End
2007-12-31
Budget Start
2006-01-01
Budget End
2006-12-31
Support Year
7
Fiscal Year
2006
Total Cost
$293,720
Indirect Cost
Name
University of California San Diego
Department
Biology
Type
Schools of Arts and Sciences
DUNS #
804355790
City
La Jolla
State
CA
Country
United States
Zip Code
92093
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