Transforming Growth Factor-Beta in Drosophila: characterization of punt and a screen for transcriptionally regulated targets.
Transforming Growth Factor-Beta (TGF-Beta) signaling mediates a wide variety of biological activities including, growth and repair processes, tissue specification, modulation of endocrine activities, and apoptosis. TGF-Beta signaling components are highly conserved evolutionarily; thus our characterization of TGF-Beta signaling in flies will contribute to a more complete understanding of this vital signaling pathway in all biological contexts. My genetic analysis of punt alleles demonstrated Punt functions throughout the fly life cycle as an oligomeric type II receptor for the Drosophila TGF-Beta homologue, Decapentaplegic (Dpp). I cloned the punt gene using the mutagenic transposon harbored in the fly line 1(3)1046 as a molecular tag. My sequence analysis revealed the punt gene product had been previously identified as Activin Receptor Type II (Atr-II) based on its homology to a mammalian activin receptor. As predicted from sequence similarity, Punt binds activin ligand. This demonstrated ability to interact with two subtypes of TGF-Beta ligands helps account, in part, for the diversity of functions mediated by TGF-Beta type II receptors. Transcriptionally regulated targets of signal transduction pathways are the ultimate effectors of signaling. I performed a screen to identify targets of dpp signaling during embryonic dorsoventral (DV) axis specification. I hypothesized since dpp activity is restricted to the dorsal 40% of the embryo, genes whose transcription is regulated by this activity will have asymmetric expression along the DV axis: genes activated by dpp will be expressed on the dorsal side of the embryo, while transcripts ventrally restricted may be suppressed by dpp, and furthermore, these transcripts may modulate dpp activity. I assayed, by whole mount in situ hybridization, the expression patterns of 798 genes during embryogenesis, and identified three genes with asymmetric DV expression, one dorsally- and two ventrally-restricted. Two have undetermined roles in dorsoventral axis specification, while the third encodes neuralized, a previously characterized ventrally restricted transcript. Just as the cloning and characterization of punt contributed to our understanding of how a TGF-Beta signal is sensed and transduced by the cell, we anticipate further characterization of these putative dorsoventral determinants will give greater insight into the cellular response to a TGF-Beta signal.
University of Utah;
Punt alleles; TGF-beta; Drosophila; Signal transduction; Genetics; Molecular Biology
Digital reproduction of “Transforming Growth Factor-Beta in Drosophila: characterization of punt and a screen for transcriptionally regulated targets.” Spencer S. Eccles Health Sciences Library. Print version of “Transforming Growth Factor-Beta in Drosophila: characterization of punt and a screen for transcriptionally regulated targets.” available at J. Willard Marriott Library Special Collection. QL3.5 2001 .S54.