The developmental basis for sensory-skeletal integration: The osteo-inductive role of neuromasts

结构与功能相结合的过程对于适应自然世界至关重要。这个过程的一个关键部分是将感觉结构（例如眼睛）与相关结构（如头骨）连接起来。不同器官系统在发育过程中相互连接的过程在很大程度上是未知的。这个项目研究了感觉系统可能影响，指导和组织脊椎动物的面部和头骨的概念，这是文献中长期怀疑的现象。经典的研究人员发现，感觉神经瘤似乎标志着未来的骨骼位置，基于现存和灭绝（化石）的证据。了解器官系统是如何整合的，对于了解适应的基本过程是必要的。拟议的工作告知不同的生理系统如何在发育过程中相互作用，并提高了我们对骨诱导的分子和发育基础的理解。这项工作将通过创造性的技术，如显微外科手术，将允许新的见解，这一经典问题进行。拟议研究的更广泛影响将扩大既定的K-12课程，向儿童传授进化论，促进国际合作和外联机会，并为本科生和研究生提供指导，以开展成功的外联活动。拟议的工作还为适应性遗传学提供了一个重要的案例研究，并创造资源，以支持更广泛的Astyanax研究社区的发展。这项应用的科学目标是了解感觉和骨骼系统之间整合的发展基础。核心假设是感觉毛细胞器官（称为“神经乳突”）诱导面部特定区域的骨形成。这个问题将通过三个目标来解决。第一个目的是检查候选诱导分子在面骨形成的关键时期的基因表达模式，以及内皮素-1信号肽功能丧失的影响，内皮素-1信号肽是面骨形成的关键分子。这些实验将确定在发育过程中何时发生诱导，以及诱导分子如何介导这种相互作用。第二个目标是使用实验移植解开神经瘤和骨骼之间的关系。完成后，这项工作将确定为什么只有某些神经管神经瘤能够诱导骨，确定神经瘤是否自主诱导骨形成，以及骨形态发生蛋白（BMP）信号传导是否介导“成骨”神经瘤的诱导特性。第三个目标将确定感觉神经瘤的实验性损失如何影响面骨形成。完成后，这项研究将确定诱导分子的神经瘤内的细胞来源。此外，这项研究将确定神经瘤是否持续表达诱导信号，周围组织是否必须能够对信号做出反应，或者两者兼而有之。通过这些研究活动，在理解结构和功能如何协调以执行基本生物过程方面有望取得重大进展。该奖项反映了NSF的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

The process of uniting structure with function is fundamentally important for adapting to the natural world. A key part of this process is connecting sensory structures (e.g. eyes) with relevant structures, like the skull. The process by which different organ systems become connected over the course of development is largely unknown. This project examines the notion that sensory systems may influence, direct and organize the face and skull of vertebrates, a phenomenon that has long been suspected in the literature. Classical researchers found that sensory neuromasts appeared to mark the future positions of bones, based on extant and extinct (fossil) evidence. Understanding how organ systems become integrated is necessary for understanding the fundamental processes governing adaptation. The proposed work informs how different physiological systems interact during development, and improves our understanding of the molecular and developmental bases for bone induction. This work will be performed through creative techniques, such as microsurgery, that will allow novel insight to this classic problem. The broader impacts of the proposed research will expand an established K-12 curriculum teaching children about evolution, promote collaboration and outreach opportunities internationally, and provide instruction for undergraduate and graduate students in developing a successful outreach activity. The proposed work also provides an essential case study for adaptive genetics, and creates resources to support growth of the broader Astyanax research community.The scientific objective of this application is to understand the developmental basis for integration between the sensory and skeletal systems. The central hypothesis is that sensory hair cell organs (called “neuromasts”) induce bone formation in specific regions of the face. This question will be approached via three aims. The first aim examines gene expression patterns of candidate induction molecules across the critical period of facial bone formation, and the impact of functional loss of the endothelin-1 signaling peptide, a key molecule for facial bone patterning. These experiments will determine when induction occurs during development, and how inductive molecules may mediate this interaction. The second aim disentangles the relationship between neuromasts and bones using experimental transplantation. When completed, this work will determine why only certain canal neuromasts are able to induce bone, determine if neuromasts induce bone formation autonomously, and if bone morphogenetic protein (BMP) signaling mediates the inductive properties of ‘osteogenic’ neuromasts. The third aim will determine how the experimental loss of sensory neuromasts impacts facial bone formation. Upon completion, this study will identify the cellular source within neuromasts of inductive molecules. Additionally, this study will determine if neuromasts continuously express an inductive signal, if the surrounding tissues must be able to respond to the signal, or both. Through these research activities, significant progress is expected towards understanding how structure and function are coordinated to execute essential biological processes.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.