Papers

Identifying the crucial lesion in a heat-induced developmental defect

M.A. Welte, I. Duncan, S. Lindquist (1995). "The basis for a heat-induced developmental defect: defining crucial lesions." Genes Dev. 9:2240-2250. Full Article

Photo: Abdomenal Defects due to heat shock Lethal heat shocks perturb a wide range of cellular processes, e.g., respiration, ion transport, DNA synthesis, and mRNA splicing. Which of these changes are the cause and which are the consequences of lethal lesions induced by elevated temperatures? To identify biologically critical targets of heat stress, we studied a developmental defect resulting from sublethal heat treatments. Such defects often are morphologically highly specific, and any particular defect typically can be induced only during narrow sensitive periods. This specificity suggests that such defects are signposts for those biological processes most sensitive to heat damage.

When Drosophila embryos are exposed to a brief heat treatment during cellularization, the resulting adult flies display homeotic transformations in their abdomen. In the photographs to the left, the upper panel shows the wild-type pattern of an abdomen, the lower the defect induced after embryonic heat treatment. Here half of the first abdominal segment (arrowhead) shows pigmentation and bristles typical of more posterior segments.

Ian Duncan had recognized that these heat-induced transformations mimic those caused by certain dominant alleles of the segmentation gene fushi tarazu (ftz ). These ftz^Ual alleles encode Ftz proteins that have increased half-lives and that accumulate to abnormally high levels. In a collaboration, we found that ftz^Ual mutations and the heat-induced defect resemble each other not only in the adult phenotype, but also by several molecular and genetic criteria, suggesting that they are caused by the same molecular lesion, overexpression of ftz. Indeed, heat shock blocks turnover of Ftz protein in tissue culture cells, heat-treated embryos appear to overexpress ftz relative to eve, and the penetrance of the heat-induced defect depends on the dosage of ftz. These results indicate that one of the most heat-sensitive processes in the cell is maintaining the correct balance of regulatory proteins.