Abstract
Developing nervous systems undergo tuning phases, called ‘critical periods’, during which nerve cells adjust their properties based on their experiences. Thus, robust nervous system function can emerge in the face of the variability that is inherent to the constituent nerve cells; and of unpredictable external influences, notably temperature, that impact on neuronal activity and metabolism. These developmental windows are termed “critical” because neuronal networks display elevated sensitivity and plasticity responses to stimuli, such that disturbances during a critical period, but not outside, can cause lasting mal-adjustment of network function. Though the impact of temperature variations on nervous system development have been well established, the underlying signalling framework remains unknown. To study this, we have harnessed a well-defined critical period of the embryo of the fruit fly, Drosophila melanogaster, and asked how heat stress experienced by the embryo leads to lasting changes to subsequent nervous system development, altering synapse size and composition, neuronal excitability and behaviour. We identified a highly conserved signalling pathway as responsible for this developmental decision window. Heat stress leads to the generation of reactive oxygen species (ROS) within mitochondria by reverse electron transport, at Complex-I of the electron transport chain. This mitochondrial ROS signal is then transmitted to the nucleus by the Drosophila homologue of the highly conserved hypoxia inducible factor-1alpha, whose activation during an embryonic critical period, but not outside this sensitive developmental window, induces lasting changes in subsequent development and function of the nervous system.
Competing Interest Statement
The authors have declared no competing interest.
Footnotes
Figure 5, figure 6 and table 1 updated. Acknowledgments updated. Few typos corrected. Few sentence changed thorught the text.
