P53-Hippo signaling regulates the dual fate of unique dental progenitors, driving mammalian jaw evolution

The mandible has undergone significant evolution, driven by two key innovations—teeth and the temporomandibular joint (TMJ)—that improved chewing efficiency and auditory function. While early vertebrates had simple, continuously replaced teeth, mammals evolved complex, specialized teeth with limited regenerative capacity. The evolutionary mechanisms and selective pressures behind this shift remain largely unknown.
This study identifies apical dental follicle progenitors as an evolutionarily acquired cell population unique to most mammals. These progenitors differentiate into distinct subpopulations that form the periodontal ligament and alveolar bone. Maintaining a precise balance between these subpopulations is crucial for the proper development of the tooth root's soft and hard tissues.
Functional parallels in the TMJ, another cranial neural crest-derived structure composed of bone and ligament, suggest shared developmental mechanisms for coordinating these tissues. Cross-species comparisons and multiomic analysis reveal that P53-Hippo signaling regulates the dual lineage fate of these progenitors. Our findings demonstrate how the emergence of new cell types drives major evolutionary changes, leading to refined physiological functions, and offer a framework for understanding the origins of other complex tissues.