Bloomquist Ryan F
Institute of Bioengineering and Biosciences, School of Biological Sciences, Georgia Institute of Technology, Atlanta, GA, USA.
School of Medicine, University of South Carolina, 6311 Garners Ferry Rd, Columbia, SC, 29209, USA.
Naturwissenschaften. 2025 Jan 27;112(1):12. doi: 10.1007/s00114-025-01964-6.
While most dentate non-mammalian vertebrates possess simple conical teeth, some demonstrate complex tooth shapes. Lake Malawi cichlid fishes are an extreme example of this, exhibiting a myriad of tooth shapes driven by an ecologically derived rapid evolution of closely related but distinct species. Tooth shape in mammals is generally considered to be established by signaling centers called primary and secondary enamel knots, which are not believed to be present in non-mammalian vertebrates. In this study, signaling centers of gene expression with epithelial folding with similar molecular patterns to that of mammalian enamel knots are identified, and differences of asymmetric gene expression are identified between fish that possess species specific polymorphisms of either bicuspid or tricuspid teeth. Gene expression is then manipulated indirectly using a small molecule inhibitor of the Notch pathway, resulting in phenotypical aberrations of tooth shape and patterning, including a mimic of a tricuspid tooth in a fish with a naturally occurring bicuspid dentition. This study provides insight into the evolutionary origins of tooth shape and advances our knowledge of the molecular determinants of dental morphology with translational utility in regenerative dentistry.
虽然大多数有齿的非哺乳动物脊椎动物都拥有简单的圆锥形牙齿，但有些则呈现出复杂的牙齿形状。马拉维湖慈鲷就是一个极端的例子，它们展现出无数种牙齿形状，这是由密切相关但又不同的物种在生态驱动下快速进化所致。哺乳动物的牙齿形状通常被认为是由称为初级和次级釉结的信号中心决定的，而人们认为非哺乳动物脊椎动物中不存在这些信号中心。在这项研究中，我们识别出了与哺乳动物釉结具有相似分子模式的、伴随上皮折叠的基因表达信号中心，并在具有双尖牙或三尖牙物种特异性多态性的鱼类之间，识别出了不对称基因表达的差异。然后，我们使用Notch信号通路的小分子抑制剂间接操纵基因表达，导致牙齿形状和图案出现表型畸变，包括在具有天然双尖牙列的鱼类中模拟出三尖牙。这项研究为牙齿形状的进化起源提供了见解，并推进了我们对牙齿形态分子决定因素的认识，对再生牙科具有转化应用价值。
