CAREER: Pulling the Mouth Open: Coordinating orofacial tissue growth and epithelial integrity to form the embryonic mouth

口腔连接消化系统和外部环境。没有这种联系，动物就不能进食。值得注意的是，尽管它显然很重要，但很少有研究讨论这种最初的联系是如何建立的。在口腔面部进化、发育和出生缺陷的研究中也不经常考虑它，在发育或解剖学教科书中也很少提到它。在这个项目中，一系列实验将确定消化系统的第一个连接是如何形成的，以及它的发展是如何与周围面部结构的形成密切相关的。具体地说，这个假设是面部的生长和紧张促使嘴巴张开。非洲爪哇的分子、细胞、胚胎学和生物力学方法将结合起来检验这一假说。根据初步数据，预计分子信号、细胞连接(如桥粒)和有丝分裂之间的新联系将被发现。这项工作具有潜在的重大影响，因为它是第一次研究：1)紧张在口腔面部发育中的作用；2)控制如何与消化系统建立联系的分子机制。此外，这项工作还纳入了一个创新的教育计划。将开设研究生和本科生水平的实验室课程，学生将在其中进行实验，为项目做出贡献。此外，VCU的少数民族项目还计划进行本科生自主学习和暑期研究项目。在教育光谱的另一端是学龄前部分，孩子们将在不同的生命阶段接触到活的青蛙，并结合艺术、数学和阅读活动。总而言之，这项工作将为几个级别的学生提供机会，帮助他们更好地了解脊椎动物的嘴发育。

The mouth connects the digestive system with the external environment. Without this connection animals cannot eat. Remarkably, despite its obvious importance, there have been few studies that address how this initial connection is established. It is also not often considered in studies of orofacial evolution, development and birth defects, and is rarely mentioned in developmental or anatomical textbooks. In this project, a series of experiments will define how the first connection to the digestive system is formed, and how its development is intimately tied to the formation of surrounding facial structures. Specifically, the hypothesis is that growth and tension within the face pulls the mouth open. Molecular, cellular, embryological and biomechanical approaches in Xenopus will be combined to test this hypothesis. Based on preliminary data it is expected that novel connections between molecular signals, cellular junctions, such as desmosomes, and mitosis will be uncovered. This work is potentially high impact in that it is the first to study: 1) the role of tension in orofacial development and 2) the molecular mechanisms governing how the connection to the digestive system is established. Additionally, this work is integrated into an innovative educational plan. Graduate and undergraduate level laboratory courses will be created where students will perform experiments contributing to the project. In addition, undergraduate independent study and summer research projects are planned for VCU's minority programs. On the opposite end of the educational spectrum is a preschool component where children will be exposed to living frogs at various life stages combined with art, math and reading activities. Together, this work will provide students at several levels with the opportunity to contribute to a better understanding of vertebrate mouth development.