Evo-Devo Regulation and Coordination of Vertebrate Dentitions and Jaws

脊椎动物牙列和颌的 Evo-Devo 调节和协调

• 批准号: RGPIN-2016-05177
• 负责人: Boughner, Julia
• 金额: $ 2.4万
• 依托单位: University of Saskatchewan
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2016
• 资助国家: 加拿大
• 起止时间: 2016-01-01 至 2017-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=615544
• 关键词: Evo; Devo; Regulation; Coordination; Vertebrate

Eating is of course essential to survival. A core question driving studies of primate, mammalian and vertebrate evolution is how different head sizes and shapes arose without compromising vital head functions and structures (e.g., teeth and the jaws that hold them). To eat, hunt, and ultimately survive to raise offspring, an animal’s teeth and jaws must develop properly in the right place, at the right time. Despite their importance for survival, the developmental-genetic processes that coordinate tooth and jaw growth remain a mystery. Explaining these processes is vital to understand how species develop, evolve and adapt to a variety of foods. In some species, including humans, teeth and jaws are also important for functions beyond eating, such as making sounds and facial expressions. Also, human tooth and jaw evolution is likely entwined with cultural evolution, notably tool-use and cooking. The long term objective of my NSERC-funded research program is to determine the extent to which dental and jaw tissues influence each other’s development and, putatively, evolution. My trainees and I will examine this question using a mouse model system where a mutation of the gene, p63, leads to the failure of teeth to develop in the jaw. By experimentally "removing teeth from the equation", already we have identified for the first time a network of genes that appear to regulate tooth formation with virtually no impact on lower jaw formation. This gene network could allow teeth to evolve without risking lethal change to the jaw skeleton. Now, we seek to determine exactly where and when these genes-of-interest are active in the embryonic tooth, and which genes in the network speak directly, or indirectly, to each other and are directed by the p63 gene, a “master regulator”. In this way, we will assemble the pieces of this particular gene regulatory network. We will use our new knowledge about where exactly in developing teeth these genes are active to experimentally determine their particular functions, which are still not known. In creating this new knowledge about the genetics of tooth formation, we will fill a long-standing gap in our collective understanding of how diversity arose among vertebrates living and extinct. My novel research program will involve training outstanding undergraduate and graduate students over the five-year funding period, providing my students with the highly-desired professional skills necessary to make them competitive for jobs in research and other Canadian career sectors such as education, government, industry and communication. We will use our unique scientific insights to more accurately model how animal faces and heads develop and evolve. In the future, we will expand our model of hard tissues (bones, teeth) to test how soft tissues such as muscles change alongside bones, allowing different species to use their mouths in specific ways to hunt or forage for a variety different food types.

吃当然是生存的必要条件。推动灵长类动物、哺乳动物和脊椎动物进化研究的一个核心问题是，不同的头部大小和形状是如何在不损害重要的头部功能和结构（例如，牙齿和支撑它们的颌）的情况下出现的。为了进食、捕猎并最终存活下来养育后代，动物的牙齿和下颚必须在正确的时间、正确的位置发育。尽管它们对生存很重要，但协调牙齿和颌骨生长的发育-遗传过程仍然是一个谜。解释这些过程对于了解物种如何发展、进化和适应各种食物至关重要。在包括人类在内的一些物种中，牙齿和颌骨除了进食之外，还具有重要的功能，比如发声和面部表情。此外，人类牙齿和下颚的进化很可能与文化进化交织在一起，尤其是工具的使用和烹饪。我的nserc资助的研究项目的长期目标是确定牙齿和颌骨组织在多大程度上影响彼此的发育和进化。我和我的学员将用一个小鼠模型系统来研究这个问题，在这个模型系统中，基因p63的突变会导致下颌牙齿发育失败。通过实验“将牙齿从方程中剔除”，我们已经首次确定了一个基因网络，它似乎调节牙齿的形成，而实际上对下颌的形成没有影响。这种基因网络可以让牙齿进化，而不会危及颌骨的致命变化。现在，我们试图确定这些相关基因在胚胎牙齿中活跃的确切位置和时间，以及网络中的哪些基因直接或间接地相互联系，并由p63基因（一个“主调节器”）指导。通过这种方式，我们将组装这个特定基因调控网络的片段。我们将利用我们关于这些基因在牙齿发育过程中活跃的确切位置的新知识，通过实验确定它们的特殊功能，这些功能目前尚不清楚。通过创造关于牙齿形成遗传学的新知识，我们将填补长期以来我们对脊椎动物多样性是如何在活着的和灭绝的脊椎动物之间产生的集体理解的空白。我的新研究项目将包括在五年的资助期内培养优秀的本科生和研究生，为我的学生提供必要的高期望的专业技能，使他们在研究和加拿大其他职业部门（如教育、政府、工业和通信）中具有竞争力。我们将利用我们独特的科学见解，更准确地模拟动物的脸和头是如何发展和进化的。未来，我们将扩展我们的硬组织（骨骼、牙齿）模型，以测试肌肉等软组织是如何随着骨骼变化的，从而允许不同物种以特定的方式使用它们的嘴来捕猎或觅食各种不同类型的食物。