In both humans and birds, parents may pass along information to help their offspring adapt to conditions in the world; some signals are transmitted even before birth, causing changes in development, physiology and behaviour that can last the entire lifespan. Recently, project partners Mariette & Buchanan (Science, 2016) discovered a highly novel example of such a process in the zebra finch (a songbird), a well-established experimental model organism for neuroscience, behaviour and genomics. Working with wild-derived birds in Australia, they found that parents pass along "weather reports"- signals that alter the developmental trajectory of their offspring so they will respond adaptively to temperature conditions upon hatching. Amazingly, these reports are delivered via vocal signals transmitted while the offspring are still in the egg. Altered developmental programming can be detected within a day after hatching as a change in the temperature dependence of growth rate and begging behaviour. Mariette & Buchanan showed that exposure to these parental signals in ovo has lifelong consequences on adaptive fitness and behaviour, leading to enhanced reproductive success of the offspring after they mature when conditions are hot. How can relatively brief exposures to an acoustic signal lead to such profound and lasting changes in development, physiology and fitness? This very basic question has broad implications, ranging from how environmental information gets transferred across generations, to how developmental pathways may be shaped and reprogrammed, and how organisms might adapt to climate change. To answer this, we will apply the extensive expertise in zebra finch genomics and neuroscience developed by the PI and his colleagues over the last three decades. First, we will determine where and how the embryo initially "hears" the incubation call. We will use techniques well established in our prior work for measuring and localizing dynamic gene activity in the zebra finch brain, to map sites in the embryo that first respond to the sound of incubation calls. Accomplishing this will establish the mechanism of primary reception for incubation call signals, and will provide a fresh look at the earliest stages of auditory development in this important model for auditory communication and learning. Second, we will test the hypothesis that incubation call exposure specifically leads to altered physiological responses to high temperatures in nestlings. This hypothesis defines a physiological output and provides a functional explanation for the evolution and maintenance of parental call-dependent reprogramming. Working with project partners in Australia (who are providing their resources, expertise and training at no cost to this BBSRC project), we will collect physiological indicators of heat tolerance (body temperature, metabolic rate, endocrine measures) in nestlings that had been exposed to incubation calls before hatching followed by chronic or acute temperature elevations in the nest. This aim also links to emerging evidence that developmental reprogramming of heat tolerance may occur in poultry. Third, to identify the regulatory mechanisms (and specific genes) that underlie the persistence of reprogramming, we will test for sustained epigenetic responses (changes in gene expression and DNA methylation) following embryonic incubation call exposure. Using a combination of high-throughput screening and targeted gene-specific methods, we will look for effects both in the whole brain and specifically in the hypothalamus, and in both embryos and older animals. Together these data will address for the first time the mechanisms underlying prenatal communication and their fundamental importance for developmental trajectories and individual fitness. In doing so our project will address the mechanisms at the heart of genotype x environment interactions, so prevalent throughout biology.