Ectopic overexpression of Drosophila lamin C is stage-specific lethal

To gain insight into the function of the developmentally regulated A-type l amins we transformed Drosophila melanogaster with a construct containing th e hsp70 promoter followed by the Drosophila lamin C (an analog of vertebrat e A-type lamins) cDNA. Lamin C was expressed ectopically after heat shock o f embryos and localized to the nucleus. No phenotypic change was observed a fter lamin C expression in embryos that normally do not contain lamin C, Ho wever, ectopic expression of lamin C during most larval (but not pupal) sta ges stalled growth, inhibited ecdysteroid signaling (in particular during t he larval-prepupal transition), resulted in development of melanotic tumors , and finally caused death. During pupation in control animals, when massiv e apoptosis of larval tissues takes place, lamin C is proteolyzed into a fr agment with a size similar to that predicted by caspase cleavage. The ectop ically expressed lamin C is identically cleaved, resulting in a large incre ase of the steady-state level of the lamin C fragment. A null mutation of t he dcp-l gene, one of the two known Drosophila caspase genes, also results in development of melanotic tumors and larval death, suggesting that the ec topically expressed lamin C inhibits apoptosis through competitive inhibiti on of caspase activity. (C) 1999 Academic Press.