Developmental reprogramming following prenatal acoustic signals

在人类和鸟类中，父母可能会传递信息，帮助他们的后代适应世界的条件；一些信号甚至在出生前就被传递，导致发育、生理和行为的变化，可能持续整个生命。最近，项目合作伙伴Mariette&Buchanan(《科学》，2016)在斑马雀(一种鸣禽)身上发现了一个非常新颖的例子，斑雀是神经科学、行为和基因组学的一种成熟的实验模式生物。研究人员在澳大利亚对野生鸟类进行研究后发现，父母会传递“天气报告”--这种信号会改变后代的发育轨迹，使其在孵化后对温度条件做出适应性反应。令人惊讶的是，这些报告是在后代还在卵子里时通过声音信号传递的。发育程序的改变可以在孵化后的一天内检测到，这是生长速度和乞讨行为的温度依赖关系的变化。Mariette&Buchanan表明，在卵子中暴露在这些父母信号中会对适应能力和行为产生终生影响，导致后代在高温条件下成熟后繁殖成功。相对短暂的声音信号暴露是如何导致发育、生理和适应能力发生如此深刻和持久的变化的？这个非常基本的问题具有广泛的影响，从环境信息如何在几代人之间转移，到如何塑造和重新编程发展路径，以及生物如何适应气候变化。为了回答这个问题，我们将应用斑马雀基因组学和神经科学方面的广泛专业知识，这些专业知识是由PI和他的同事在过去30年中开发的。首先，我们将确定胚胎最初在哪里以及如何“听到”孵化呼唤。我们将使用我们先前工作中成熟的技术来测量和定位斑雀大脑中的动态基因活动，以绘制胚胎中首先对孵化呼唤做出反应的位置。这将建立孵化叫声信号的初级接收机制，并将提供一个新的视角，在这一重要的听觉交流和学习模型中，听觉发育的早期阶段。第二，我们将检验孵化叫声暴露专门导致雏鸟对高温的生理反应改变的假设。这一假说定义了一种生理输出，并为父母依赖于呼叫的重编程的进化和维持提供了功能解释。与澳大利亚的项目合作伙伴(他们免费为BBSRC项目提供资源、专业知识和培训)合作，我们将收集在孵化前暴露在孵化呼叫中的雏鸟的耐热生理指标(体温、代谢率、内分泌指标)，这些雏鸟在孵化前经历了慢性或急性的温度升高。这一目的也与新出现的证据相联系，即热耐性的发育重新编程可能发生在家禽中。第三，为了确定重新编程持续存在的调节机制(和特定基因)，我们将测试胚胎孵化呼叫暴露后的持续表观遗传反应(基因表达和DNA甲基化的变化)。使用高通量筛选和靶向基因特异性方法的组合，我们将在整个大脑中寻找影响，特别是在下丘脑，在胚胎和老年动物中。这些数据将首次涉及产前沟通的潜在机制及其对发育轨迹和个体健康的根本重要性。在这样做的时候，我们的项目将解决在整个生物学中普遍存在的基因x环境相互作用的核心机制。

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.