Molecular Regulatory Mechanism of Mesenchymal Stem Cells in Adult Mouse Incisors

Stem cells are remarkable. They form tissues during development, maintain tissue homeostasis and perform injury repair in adults. The mouse incisor provides an excellent model for stem cell study because it grows continuously throughout life. Stem cells residing in the proximal region of the incisor in adult mice can replenish all incisor cells within one month. We have recently shown that the mesenchymal stem cells (MSCs) in the adult mouse incisor are a Gli1+ cell population surrounding the neurovascular bundle (NVB) near the cervical loop region and that they govern tissue homeostasis and repair. The NVB secretes Shh and provides a niche for MSCs in the incisor. However, the functional significance of Shh secreted from the sensory nerve within the NVB still needs to be investigated. During normal homeostasis, MSCs exit from their niche and become transit-amplifying (TA) cells, undergoing a series of divisions before terminal differentiation. The transition process from MSC to TA cell is a common feature in diverse organs but little is known about the presumably complex signaling network that governs this transition. Based on our data and taking advantage of well-established animal models, we hypothesize that: 1. secretion of Shh by the sensory nerve supports MSCs in the adult mouse incisor and that 2. Wnt signaling and Wnt/Bmp interactions control the MSC to TA cell transition and the fate of MSCs to maintain mesenchymal cell homeostasis in the adult mouse incisor.