Cofilin-Mediated Actin Stress Response Is Maladaptive in Heat-Stressed Embryos

Environmental stress threatens the fidelity of embryonic morphogenesis. Heat, for example, is a teratogen. Yet how heat affects morphogenesis is poorly understood. Here, we identify a heat-inducible actin stress response (ASR) in Drosophila embryos that is mediated by the activation of the actin regulator Cofilin. Similar to ASR in adult mammalian cells, heat stress in fly embryos triggers the assembly of intra-nuclear actin rods. Rods measure up to a few microns in length, and their assembly depends on elevated free nuclear actin concentration and Cofilin. Outside the nucleus, heat stress causes Cofilin-dependent destabilization of filamentous actin (F-actin) in actomyosin networks required for morphogenesis. F-actin destabilization increases the chance of morphogenesis mistakes. Blocking the ASR by reducing Cofilin dosage improves the viability of heat-stressed embryos. However, improved viability correlates with restoring F-actin stability, not rescuing morphogenesis. Thus, ASR endangers embryos, perhaps by shifting actin from cytoplasmic filaments to an elevated nuclear pool. [Display omitted] •Drosophila embryos mount an actin stress response (ASR) against heat stress•Cofilin mediates the ASR, affecting actin in both the nucleus and the cytoplasm•In nuclei, actin rods assemble; in cytoplasm, F-actin structures are destabilized•F-actin destabilization disrupts morphogenesis, and embryo ASR is overall maladaptive Figard et al. show that heat stress induces an actin stress response (ASR) in early Drosophila embryos. This ASR is mediated by a heat-induced increase in Cofilin activity. Increased Cofilin activity destabilizes F-actin structures required for morphogenesis. In addition, the Cofilin-mediated ASR reduces embryo viability.