Elevated temperature fatally disrupts nuclear divisions in the early Drosophila embryo.

Temperature variations challenge animal survival, with elevated temperatures presenting distinct vulnerabilities throughout the animal life cycle. Embryonic development is especially vulnerable, though molecular mechanisms remain unclear. We address this in Drosophila melanogaster, an insect model with extensively characterized embryonic development. Here we show that pre-gastrulation development - syncytial blastoderm formation and cellularization - is particularly vulnerable to elevated temperature. Embryos exposed to elevated temperature during this period exhibit gastrulation defects and increased lethality. We observe mitotic failures causing loss of cortical nuclei during cellularization, preceded by a local nuclear crowding and increased division asynchrony; both features cooperatively amplify mitotic failures, leading to blastoderm holes. Mitotic failures trigger DNA damage response due to weakened cytoskeletal interaction. Genetic rescue experiments support the hypothesis that cortical F-actin and astral microtubule interaction is disrupted at elevated temperatures, causing mitotic failures. We propose that expression levels of corresponding genes could predict how increasing temperature variations affect insect populations.