Understanding the mechanisms that control tooth replacement

作为一个孩子，掉牙是一件值得庆祝的事情，因为牙仙子会来拜访。在以后的生活中，牙齿脱落成为一个重要的问题，伴随着种植体、桥和假牙的前景。这是因为作为哺乳动物，我们只有两副牙齿，乳牙和恒牙。这就带来了一个问题，为什么我们有这种限制，而在动物界的其他地方，鲨鱼、蛇和鳄鱼似乎有无限的替代牙齿供应。在这里，我们的目标是通过研究决定牙齿是否被替换的信号来了解限制哺乳动物牙齿数量的机制。为此，我们将研究一种不更换牙齿的动物（老鼠）和一种更换部分牙齿的哺乳动物（负鼠），并将其与不断更换牙齿的爬行动物（玉米蛇）和只有一套牙齿的爬行动物（变色龙）进行比较。我们之前已经证明，在老鼠身上，第一颗牙齿会抑制替代牙齿的形成。这里我们问的是这些信号是什么（目标1）。我们知道负鼠相邻的牙齿有不同的替代能力，但我们不知道是什么导致了这些差异，使一颗牙齿替代，另一颗牙齿不替代（目标2）。蛇的牙齿在紧密排列的链中相互替换，因此在哺乳动物中观察到的抑制作用不会发生。哺乳动物在进化过程中发生了什么变化？哺乳动物中限制牙齿数量的信号是否在有齿动物中是共享的，或者哺乳动物与爬行动物相比，牙齿替换的规则是否不同（ai3）。这些知识将为理解控制牙齿替换策略的机制提供基础，为将来控制牙齿数量提供可能性。例如，如果我们了解第一颗牙齿如何抑制替代牙齿并导致其恶化，我们就可以防止这种情况发生，并重新唤醒牙齿替代的潜力。这对于那些在动物寿命结束前无法替换的恒牙恶化的情况尤其重要。

As a child losing a tooth is a cause for celebration with a visit from the tooth fairy. Later in life, tooth loss becomes a significant issue, with the prospect of implants, bridges, and dentures. This is because as mammals we only have two sets of teeth, our baby (deciduous) teeth, and our permanent teeth. This brings the question of why we have this restriction when elsewhere in the animal kingdom sharks, snakes and crocodiles have a seemingly unlimited supply of replacement teeth. Here we aim to understand the mechanisms that restrict tooth number in mammals by investigating the signals that determine whether a tooth is replaced or not. For this, we will study replacement in an animal that does not replace its teeth (the mouse) and a mammal that replaces some of its teeth (the opossum) and compare to a reptile that constantly replaces its teeth (the corn snake) and a reptile that only has one set of teeth (the chameleon). We have previously shown that in the mouse the first tooth inhibits the formation of a replacement tooth. Here we ask what those signals are (Aim 1). We know that neighbouring teeth in the opossum have different replacement capacity but we don't know what drives these differences, to make one tooth replace and one tooth not (Aim 2). Snake teeth replace each other in a tightly packed chain, so the inhibition observed in mammals doesn't occur. What changed during the evolution of mammals? Are the signals that restrict tooth number in mammals shared across toothed animals or are the rules for tooth replacement distinct in mammals compared to reptiles (Aim3). This knowledge will provide the foundation for an understanding of the mechanisms that control tooth replacement strategies, providing the possibility of controlling tooth numbers in the future. For example, if we understood how the first tooth inhibits the replacement tooth and causes its deterioration, we could prevent this from happening and reawaken tooth replacement potential. This will be particularly important in instances where non-replacing permanent teeth deteriorate prior to the end of an animal's lifespan.