Role of Activin Signaling in Neuronal Development

Sequencing of the Drosophila genome has enabled identification of all TGF-ß superfamily ligands, their receptors and cytoplasmic signal transducers. In sum, a total of only 7 ligands act through 2 type II receptors, 3 type I receptors and 3 Smads. Three previously identified ligands, Dpp, Scw and Glass bottom boat represent the BMPs. Four new ligands dActivin, Myoglianin (a homolog of vertebrate Myostatin), Dawdle (Daw) and Maverick, have been identified that potentially represent an emerging activin pathway in flies (Parker et al, 2003). We are interested in isolating mutations in these genes and characterizing their role in development and differentiation. Unlike BMPs that are required for early embryonic patterning, several of the newly identified activin-related ligands are expressed in post-mitotic embryonic and larval neurons. This suggests that activin signaling is likely to have important roles in neuronal function and behavior, consistent with our analysis of mutations in the daw gene (Parker et al., 2006). In addition to understanding the role of individual ligands, an important conceptual problem we are interested in is how related ligands expressed in overlapping sets of neuronal cells maintain signaling specificity and reduce the potential for crosstalk.

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