Sylvia presenting her work at SICB 2020
Another SICB, another great presentation from Sylvia Nunez from Thom Sanger’s lab investigating how the interaction between heat and oxygen availability affects development in the brown anole (Anolis sagrei). Last year, Sylvia presented a poster showing that above 33°C, embryonic survival was greatly reduced and many embryos developed craniofacial malformations. With some potential nesting sites for anoles now exceeding 40°C, understanding mechanisms leading to decreased survival is critical.
Low oxygen at sublethal temperatures can recapitulate negative effects on craniofacial development at high temperatures.
As a follow up to this study, Sylvia set out to understand exactly how it is that heat and oxygen can interact to lead to craniofacial deformities. She posited several hypotheses and was able to eloquently test each one, including the neural degeneration hypothesis and the oxygen limitation hypothesis. Specifically, Sylvia noted that disruption in sonic hedgehog has been linked to facial development and that oxygen demand can often exceed oxygen supply at high temperatures.
First, Sylvia tested the oxygen limitation hypothesis by examining whether low oxygen coupled with sublethal (elevated) temperature conditions recapitulate the effects of craniofacial malformation under thermal stress. Previous work in the lab induced craniofacial malformation at 36°C; Sylvia showed you could mimic this effect using 33°C with low oxygen, with a greater rate of malformation than in 27°C (the standard control temperature) with atmospheric oxygen, 27°C with low oxygen, or 33°C with atmospheric oxygen. She then tested whether an increase in oxygen can rescue embryonic survival at high temperatures. To do so, she split eggs among two treatment conditions: 27°C with high oxygen and a hot nest site temperature with high oxygen. She found further support for the oxygen limitation hypothesis – when oxygen availability was increased above atmospheric conditions there were no differences in embryonic survival. Wow! Further, there were no craniofacial malformations in the high temperature treatment when oxygen conditions were high.
To follow up on this finding, she examined if oxidative stress could be the link between temperature and craniofacial malformations using superoxide dismutase (SOD), an enzyme that helps turn the superoxide radical (O2–) into oxygen (O2) or hydrogen peroxide (H2O2), as a marker for oxidative stress in the telencephalon. Indeed, within mere minutes of a temperature increase, SOD becomes upregulated, suggesting that thermal stress contributes to oxidative stress. But Sylvia didn’t stop there. She then treated some embryos with an SOD inhibitor to show that when SOD is absent craniofacial malformations appear.
Overall, Sylvia has very eloquently shown that increased temperature leads to craniofacial malformations via thermal effects on oxidative stress. I cannot wait to see what she presents next year!