We present evidence that the JAK-STAT signal transduction pathway regulates multiple developmental processes in Drosophila. We screened for second-site mutations that suppress the phenotype of the hyperactive hop(Tum- l) Jak kinase, and recovered a mutation that meiotically maps to the known chromosomal position of D-Stat, a Drosophila stat gene. This hypomorphic mutation, termed stat(HJ), contains a nucleotide substitution in the first D- Stat intron, resulting in a reduction in the number of correctly processed transcripts. Further, the abnormally processed mRNA encodes a truncated protein that has a dominant negative effect on transcriptional activation by the wild-type cDNA in cell culture. stat(HJ) mutants exhibit patterning defects that include the formation of ectopic wing veins, similar to those seen in mutants of the epidermal growth factor/receptor pathway. Abnormalities in embryonic and adult segmentation and in tracheal development were also observed. The hop(Tum-l) and stat(HJ) mutations can partially compensate for each other genetically, and Hop overexpression can increase D- Stat transcriptional activity in vitro, indicating that the gene products interact in a common regulatory pathway.
Yan, R., Luo, H., Darnell, J. E., & Dearolf, C. R. (1996). A JAK-STAT pathway regulates wing vein formation in Drosophila. Proceedings of the National Academy of Sciences of the United States of America, 93(12), 5842–5847. https://doi.org/10.1073/pnas.93.12.5842