Drosophila Lyra mutations are gain-of-function mutations of senseless

The Lyra mutation was first described by Jerry Coyne in 1935. Lyra causes r ecessive pupal lethality and adult hetrrozygous Lyra mutants exhibit a domi nant loss of the anterior and posterior wing margins. Unlike many mutations that cause loss of wing tissue (e.g., scalloped, Beadex, cut, and apterous -Xasta, Lyra wing discs do not exhibit increased necrotic or apoptotic cell death, nor do they show altered BrdU incorporation. However, during wing d isc eversion, loss of the anterior and posterior wing margins is apparent. We have previously shown that senseless, a gene that is necessary and suffi cient for peripheral nervous system (PNS) development, is allelic to Lyra. Here we show by several genetic criteria that Lyra alleles are neomorphic a lleles of senseless that cause ectopic expression of SENSELESS in the wing pouch. Similarly, overexpression of SENSELESS in die wing disc causes loss of wing margin tissue, thereby mimicking the Lyra phenotype. Lyra mutants d isplay aberrant expression of DELTA, VESTIGAL, WING LESS, and CUT. As in Ly ra mutants, overexpression of SENSELESS in some areas of the wing pouch als o leads to loss of WINGLESS and CUT. In summary, our data indicate that ove rexpression of SENSELESS causes a severe reduction in NOTCH signaling that in turn may lead to decreased transcription of several key genes required f or wing development, leading to a failure in cell proliferation and loss of wing margin tissue.