EYES ABSENT and TIMELESS integrate photoperiodic and temperature cues to regulate seasonal physiology in Drosophila

Abstract

<jats:p>Organisms possess photoperiodic timing mechanisms to detect variations in day length and temperature as the seasons progress. The nature of the molecular mechanisms interpreting and signaling these environmental changes to elicit downstream neuroendocrine and physiological responses are just starting to emerge. Here, we demonstrate that, in<jats:italic>Drosophila melanogaster</jats:italic>, EYES ABSENT (EYA) acts as a seasonal sensor by interpreting photoperiodic and temperature changes to trigger appropriate physiological responses. We observed that tissue-specific genetic manipulation of<jats:italic>eya</jats:italic>expression is sufficient to disrupt the ability of flies to sense seasonal cues, thereby altering the extent of female reproductive dormancy. Specifically, we observed that EYA proteins, which peak at night in short photoperiod and accumulate at higher levels in the cold, promote reproductive dormancy in female<jats:italic>D. melanogaster</jats:italic>. Furthermore, we provide evidence indicating that the role of EYA in photoperiodism and temperature sensing is aided by the stabilizing action of the light-sensitive circadian clock protein TIMELESS (TIM). We postulate that increased stability and level of TIM at night under short photoperiod together with the production of cold-induced and light-insensitive TIM isoforms facilitate EYA accumulation in winter conditions. This is supported by our observations that<jats:italic>tim</jats:italic>null mutants exhibit reduced incidence of reproductive dormancy in simulated winter conditions, while flies overexpressing<jats:italic>tim</jats:italic>show an increased incidence of reproductive dormancy even in long photoperiod.</jats:p>

Neuroendocrine Regulation of Reproductive Dormancy in the Fruit Fly Drosophila melanogaster: A Review of Juvenile Hormone-Dependent Regulation

“…Knockdown of eya in IPCs causes an increase in the size of the ovary, implying that Eya negatively regulates oogenesis through IPCs. Interestingly, the expression of eya has a circadian rhythm (Abrieux et al, 2020). More precisely, the peak of Eya protein levels is delayed in the short-day condition in comparison to the long-day condition.…”

“…This fact implies that reproductive dormancy in D. melanogaster has both quiescence and diapause properties. Therefore, most papers published in recent years simply use "dormancy" to describe the short-day and low temperatureinduced changes in D. melanogaster adults (Kubrak et al, 2016;Liu et al, 2016;Andreatta et al, 2018;Lirakis et al, 2018;Ojima et al, 2018;Nagy et al, 2019;Abrieux et al, 2020). In this paper, as is customary, we will refer to the D. melanogaster phenotypes in terms of dormancy.…”

“…Besides the regulation mediated by the central clock pacemaker neurons, the activity of IPCs is also regulated by transcription regulators expressed in IPCs. This mechanism has been revealed in a study on a gene called eyes absent (eya) (Abrieux et al, 2020). Eya encodes a highly conserved transcriptional coactivator and protein phosphatase that plays vital roles in multiple developmental processes in organisms ranging from Drosophila to humans.…”

Peripheral Sensory Organs Contribute to Temperature Synchronization of the Circadian Clock in Drosophila melanogaster

“…Even lower temperatures (<14°C) in combination with short photoperiods induce diapause or reproductive dormancy in D. melanogaster ( Saunders and Gilbert, 1990 ). It has recently been shown that accumulation of the cotranscription factor EYES ABSENT (EYA) is required for an efficient transition to female diapause ( Abrieux et al, 2020 ). Interestingly, TIM-SC is the major Tim isoform under 10°C, and presumably binds to, and stabilizes EYA under these conditions, thereby promoting diapause entry.…”

The Eyes Absent proteins in development and in developmental disorders

“…The tyrosine phosphatase-dead form of EYA3 was able to potentiate TEF/SIX1-mediated TSHβ transcription to levels comparable to the wild-type protein [ 58 ], suggesting that the tyrosine phosphatase activity is dispensable for EYA3's role in photoperiodism. Collectively, the currently available evidence supports a role for EYA3's transactivation activity in measuring night length and tuning the circadian clock with seasonal changes [ 60 ].…”