In a warming world, all life forms - endotherms and ectotherms alike - are finding their homeostasis being challenged. The environmental change is challenging at all stages of life. How different organisms tune their homeostasis at various life stages to manage these environmental insults is an unanswered question. Complex multicellular organisms, such as the ones we can see with the naked eye, accommodate temperature extremes through a variety of responses, including, but not limited to, sweating, increased respiration, seeking shelter, shivering and communal warming. However, as we can imagine, such responses are not possible at embryonic stages, making them more vulnerable to temperature shifts.
How then do embryos manage the temperature extremes? It is likely that embryos employ rather conserved cell biological responses, such as changes in metabolism, to try and ensure survival. Such metabolic changes could, in turn, be readily achieved through changes in the transcriptomic state of a cell. Even though this strategy might seem likely, we also need to keep in mind that unchecked shifts in the transcriptome can derail normal developmental programs through, say, changes in cell fate specification. There is also a growing body of literature describing the link between metabolism and embryonic developmental programs (Cao et al., 2024; Stapornwongkul et al., 2025). Thus, adaptation to temperature extremes could introduce trade-offs, and understanding such trade-offs is crucial to predict what can go wrong while an organism is preparing its response to environmental warming. A recent preprint (O'Leary et al., 2025 preprint) is tackling this question, using a multiomics approach to quantify homeostatic shifts in chromatin accessibility and concomitant transcriptional changes due to temperature acclimation in Drosophila melanogaster: a model organism that boasts a detailed understanding of its embryonic development, at the genetic level.
To begin with, O'Leary and colleagues ask an important question: how does embryo survival at high temperatures relate to their acclimation temperature? After acclimating embryos to 18, 25 or 30°C, the embryos were exposed to an acute heat shock (38.5°C for 45 min). As one might expect, embryos acclimated to 30°C performed the best. However, even more interesting was the difference in survival between 18 and 25°C. Despite both 18 and 25°C being within the normal range of temperatures for Drosophila embryos, the embryo acclimated to 18°C showed unexpectedly poor survival. This led the authors to ask whether there was something special about acclimation at 18°C that hampered the performance of embryos so severely as compared to that at 25°C.
Given the differences in survival, the authors asked whether there were inherent differences in the development itself, which dictated the differences in embryo survival between 18 and 25°C. Here, the authors decided to take a multiomics approach, using ATAC-seq to assess chromatin accessibility and RNA-seq to assess the transcriptomic status of individual cells (nuclei) from multiple embryos, both at 18 and 25°C. The complementarity of these two techniques allowed the authors to 'double check' the status of entire gene regulatory networks, whether active or silenced. The authors then used these differentially active gene regulatory networks to assess any potential changes in, say, cell fate specification or metabolic reprogramming.
The authors assessed the differences in developmental programs at the level of gene regulatory networks that specify cell fates and found that the development was, perhaps unsurprisingly, similarly robust at both 18 and 25°C. However, there were also a few differences, which the authors found intriguing. For one, the chromatin was, overall, more accessible at 18°C, indicating a tendency to produce more mRNA. Then, several ribosomal protein genes were upregulated at 18°C, along with those involved in oxidative phosphorylation and those regulating transcription through RNA polymerase III. Presumably, this is a response to slower metabolism at 18°C, and authors argue that such responses might lead to higher protein production, partially accelerating the development. As we can imagine, such a shift in homeostasis is bound to improve the fitness, allowing the species to develop at a faster pace compared with those that don't engage such compensatory mechanisms.
Could this acclimation at 18°C, however, also introduce a trade-off? Authors decided to entertain the possibility that the improved fitness at lower temperature due to the acclimation response might render embryos more vulnerable to an upcoming sudden increase in temperature, i.e., a heat shock. Though, before going further, let's first address whether such a sudden change in temperature is possible in nature. If not, then one might question the need, beyond scientific curiosity, for testing the trade-offs due to acclimation at 18°C. In fact, there are previous observations and experiments that have addressed whether such an acute temperature jump occurs in nature, and found it rather common. A rotting fruit - the typical egg lay site for the fruit flies - can easily heat up when exposed to the sunlight (Feder et al., 1997). Sudden exposure to sunlight is rather common, indicating that experiencing such a sudden increase in temperature must be ubiquitous. Of note, exposure to high temperature during embryo development is not unique to fruit flies; experiencing high temperature during embryonic development (due to maternal fever) has also been linked to birth defects in humans (Edwards, 2006; Graham, 2020). This indicates that experiencing variations in temperature might be as natural as the organismal development itself, increasing the importance of addressing the trade-off between sudden temperature increase versus acclimation to lower temperature.
A sudden increase in temperature can disrupt cold-acclimated physiology in different ways. First, the normal heat shock response, which acts to accommodate the increased protein denaturation at high temperature, will be overwhelmed due to the increased abundance of proteins. Secondly, the jump in temperature would speed-up various complex biochemical reactions in a cell, including transcription and translation, which will worsen the first problem. Additionally, the turned up oxidative phosphorylation could increase the production of reactive oxygen species and oxidative damage. It is also likely that the limited nutritional storage of the embryo might be crucially depleted due to the global uptick in metabolism, without which subsequent development will fail, even if the embryo were to survive this environmental insult.
Increasingly, researchers are trying to understand how organisms will manage the challenge of a warming world. Previous studies have focused on the seasonality of allele frequencies (Rudman et al., 2022) and related them to survival in fruit flies. Additional literature focusing on the effect of acclimation in adults on the changes in embryonic gene expression and survival is also in preparation (Biel et al., 2025 preprint). O'Leary and colleagues add an important cornerstone, attacking the problem from the angle of potentially maladaptive trade-offs, reducing embryo survival at high temperature due to a prior acclimation at a colder temperature. This study also hints towards mechanisms that might naturally limit the species abundance in winter months, and warns us how species might go extinct due to intensifying temperature fluctuations.
I thank Steffen Lemke and the members of the Zoology department at the University of Hohenheim for an exciting scientific environment, and FlyBase for its crucial support that makes Drosophila research possible.