ALP23B, a novel member of the TGF-b superfamily. L. Parker ¹, M. Nguyen ¹, J. Duncan ², K. Arora ¹. 1) Developmental and Cell Biology, UC Irvine, Irvine, CA; 2) Program in Molecular Biology, University of Southern California, CA.

   The transforming growth factor-b (TGF-b) superfamily is a large group of secreted ligands which facilitate cell-cell signaling. They have been implicated in numerous processes including cell proliferation, cell death, and determination of cell fate. Three major subgroups exist, identified by sequence homology; BMPs, (bone morphogenetic proteins), activins and archetypal TGF-bs. We have identified a novel member of the TGF-b superfamily of ligands, ALP23B (Activin Like Protein at 23B). Initial molecular characterization reveals that ALP23B shows low levels of homology (approx. 30%) to each of the major subgroups of ligands, although it has the 9 cysteine residues characteristic of the activins and TGF-bs. This raises the possibility that it could bind to either BMP or activin type I receptors. Previously identified Drosophila ligands belong to either the BMP or activin subgroups, with the exception of Maverick (Nguyen et al. 2000, Mech. Dev.), which also shows low level similarity to all three subgroups. The biological role of the BMP-like ligands Dpp, Scw, and Gbb-60A is well established, however the role of the activin-like ligands, dActivin and Myoglianin, has not been investigated. We are using reverse genetic approaches such as misexpression of a dominant-negative form of ALP23B, and ds-RNA interference, to eliminate endogenous product and analyze the requirement of ALP23B in a stage specific manner. In addition, we are carrying out a screen for deletions and EMS-induced point mutations affecting ALP23B expression. We will use such alleles to induce somatic and germline clones, in order to assess the consequences of loss of ligand activity in a broad range of tissues and stages. Knowledge of the pathway that transmits the ALP23B signal can be used to elucidate similar pathways in vertebrates, and will add to a growing understanding of the role of activin-mediated pathways in the development of many species.