Characterizing the Developmental Role and Signaling Specificity of a Novel TGF-Beta Related Ligand.

University Of California-Irvine, Irvine CA

Investigators

Abstract

0131736 Arora A fundamental feature of growth and differentiation in multicellular organisms is the ability of one group of cells to influence the fate of another through intercellular communication. Thus understanding how signaling activity is regulated and modulated contributes to an important aspect of developmental biology. A long-term goal of our research is to understand the in vivo roles and mechanism of Transforming Growth Factor-B (TGF-B) signaling during development in Drosophila. Ligands of the TGF-B superfamily control a wide range of biological functions such as cell proliferation, axial patterning, tissue specification and morphogenesis in systems as diverse as worms, flies, frogs, and mice. Despite the evolutionary distance, many components of the TGF-B signaling pathway show remarkable functional conservation. Thus studies in a genetically tractable organism like Drosophila can provide crucial insights into aspects of TGF-B signaling that are relevant to both basic and clinical science. One key issue is understanding how multiple ligands expressed in the same tissue can act through a relatively limited number of receptors and downstream signal transducers to elicit a variety of biological effects. This proposal focuses on characterizing the mutant phenotype, and determining the signaling pathway utilized by a novel ligand Alp. Since Alp is equally related to the Activin/TGF-B and BMP subfamilies, it cannot be definitively assigned to a functional pathway based on structural similarity alone. Molecular and genetic approaches will be used to determine the functional requirement for alp, study how it generates spatial pattern, and identify the proteins required for its signal-transduction.