Developmental reprogramming following prenatal acoustic signals

在人类和鸟类中，父母可能会传递沿着信息，以帮助他们的后代适应世界上的条件;一些信号甚至在出生前就已经传递，导致发育，生理和行为的变化，这些变化可以持续整个生命周期。最近，项目合作伙伴Mariette & Buchanan（Science，2016）在斑胸草雀（一种鸣禽）中发现了这种过程的一个非常新颖的例子，斑胸草雀是神经科学，行为和基因组学的一种成熟的实验模型生物。他们在澳大利亚研究了野生鸟类，发现父母会传递沿着“天气报告”--改变后代发育轨迹的信号，使它们在孵化时对温度条件做出适应性反应。令人惊讶的是，这些报告是通过声音信号传递的，而后代仍然在蛋中。改变的发育编程可以在孵化后一天内检测到的变化，在温度依赖性的生长速度和乞讨行为。Mariette和Buchanan表明，在卵中暴露于这些父母信号对适应性健康和行为有终身的影响，导致后代在成熟后在炎热的条件下提高繁殖成功率。相对短暂的声音信号暴露如何导致发育，生理和健康方面如此深刻和持久的变化？这个非常基本的问题具有广泛的影响，从环境信息如何在世代之间传递，到发育途径如何形成和重新编程，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PI及其同事在过去三十年中开发的斑胸草雀基因组学和神经科学方面的广泛专业知识。首先，我们将确定胚胎最初在哪里以及如何“听到”孵化呼叫。我们将使用在我们先前的工作中建立的技术来测量和定位斑胸草雀大脑中的动态基因活性，以绘制胚胎中首先对孵化呼叫声音做出反应的位点。完成这一任务将建立孵化呼叫信号的主要接收机制，并将提供一个新的视角，在这个重要的听觉交流和learning.Second模型的听觉发展的最早阶段，我们将测试的假设，孵化呼叫曝光专门导致改变生理反应的雏鸟高温。这个假说定义了一个生理输出，并提供了一个功能解释的演变和维护父母的呼叫依赖性重编程。我们将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，收集雏鸟耐热性的生理指标（体温，代谢率，内分泌测量），这些雏鸟在孵化前暴露于孵化呼叫，然后在巢中慢性或急性温度升高。这一目标也链接到新出现的证据表明，发育重编程的耐热性可能会发生在poulct.Third，以确定的监管机制（和特定的基因），重新编程的持久性，我们将测试持续的表观遗传反应（基因表达和DNA甲基化的变化）胚胎孵化呼吁曝光。使用高通量筛选和靶向基因特异性方法的组合，我们将在整个大脑和下丘脑中，以及胚胎和老年动物中寻找效果。这些数据将首次解决产前沟通的机制及其对发展轨迹和个人健康的根本重要性。在这样做的过程中，我们的项目将解决基因型x环境相互作用的核心机制，在整个生物学中非常普遍。

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.