Hsp70 and thermal pretreatment mitigate developmental damage caused by mitotic poisons in Drosophila

Abstract

To assess the ability of the heat-inducible molecular chaperone heat-shock protein 70 (Hsp70) to mitigate a specific developmental lesion, we administered the antimicrotubule drugs vinblastine (VB) and colchicine (COL) to larvae of Drosophila engineered to express differing levels of Hsp70 after heat pretreatment (HP). VB and COL decreased survival during metamorphosis, disrupted development of the adult eye and other structures as well as their precursor imaginal disks, and induced chromosome nondisjunction in the wing imaginal disk as indicated by the somatic mutation and recombination test (SMART) assay. Hsp70-inducing HP reduced many of these effects. For the traits viability, adult eye morphology, eye imaginal disk morphology, cell death in the eye imaginal disks, and single and total mutant clone formation in the SMART assay, HP reduced the impact of VB to a greater extent in Drosophila with 6 hsp70 transgenes than in a sister strain from which the transgenes had been excised. Because the extra-copy strain has higher levels of Hsp70 than does the excision strain but is otherwise almost identical in genetic background to the excision strain, these outcomes are attributable to Hsp70. The hsp70 copy number had a variable interaction with HP and COL administration.

An Assay to DetectIn VivoY Chromosome Loss inDrosophilaWing Disc Cells

“…Although approximately 80% of the clones (50/63) appeared in the expected I-IV size classes, several grew unusually large and were assigned to classes V and VI (Table 1). This indicates that colchicine induces cell death in the wing primordia followed by intercalary regeneration, in agreement with previous data documenting that cells die most likely through the induction of aneuploidy (Isaenko et al 2002). …”

Embryo stability and vulnerability in an always changing world

“…In contrast, HSPs are not induced in response to stress during early cleavage stages of the orphan embryos (41). This strategy may be in part because overexpression of these proteins in embryos inhibits development (42), possibly by interfering with mitosis or signaling (43,44). Instead the strategy is to have adequate, but not excessive, HSP present in the egg at fertilization.…”

Effect of heat shock, pretreatment and hsp70 copy number on wing development in Drosophila melanogaster

“…Few studies, however, have examined inducible thermotolerance of development per se . In Drosophila , PT reduces the incidence of forked and hooked bristle phenocopies (Petersen & Mitchell 1991), and also enhances resistance of development to the teratogenic effects of the mitotic poisons vinblastine and colchicine (Isaenko et al . 2002).…”