Evo-Devo Regulation and Coordination of Vertebrate Dentitions and Jaws

吃当然是生存所必需的。推动灵长类、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骨)的情况下产生的。为了进食、狩猎，并最终存活下来养育后代，动物的牙齿和下巴必须在正确的地点、正确的时间正确发育。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。解释这些过程对于理解物种如何发展、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，牙齿和下巴对饮食以外的功能也很重要，比如发出声音和面部表情。此外，人类牙齿和下巴的进化可能与文化进化交织在一起，特别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相互影响彼此发育的程度，以及推测的进化。我和我的受训者将使用小鼠模型系统来研究这个问题，在小鼠模型系统中，p63基因的突变会导致牙齿在颌骨中发育失败。通过实验“从方程式中移除牙齿”，我们已经首次确定了一个基因网络，这些基因似乎调节牙齿的形成，而实际上对下颌骨的形成没有影响。这种基因网络可以让牙齿进化，而不会冒着颌骨发生致命变化的风险。现在，我们试图准确地确定这些感兴趣的基因在胚胎牙齿中何时何地活跃，以及网络中哪些基因直接或间接地相互对话，并由p63基因(一种主调节基因)指导。通过这种方式，我们将组装这个特殊的基因调控网络的片段。我们将使用我们的新知识，即这些基因在牙齿发育中的确切位置是活跃的，以实验地确定它们的特定功能，这些功能仍然未知。在创造这种关于牙齿形成遗传学的新知识时，我们将填补我们集体理解中的一个长期空白，即物种多样性是如何在现存和灭绝的脊椎动物中产生的。我的创新研究计划将包括在五年的资助期内培养优秀的本科生和研究生，为我的学生提供所需的高度期望的专业技能，使他们在研究和其他加拿大职业领域的工作中具有竞争力，如教育、政府、工业和通信。我们将使用我们独特的科学见解来更准确地模拟动物的面部和头部是如何发育和进化的。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如何与骨骼一起变化，允许不同物种以特定方式使用嘴巴来狩猎或寻找各种不同的食物类型。

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.