Removing Ptpn11 (SHP2) Leads to a Lack of Tooth Roots

Objectives: Recent studies identified a set of genes (such as Nfic, Osx and b-catenin), that control the formation of the tooth root but not the crown. These findings not only challenge the current dogma but raise a strong need for identifying more genes in order to understand the mechanism of tooth root formation. We and other laboratories have studied the role of Ptpn11 (encoding the Src homology-2 domain containing protein tyrosine phosphatase-2, SHP2), which couples growth factor receptors to activate the Ras/Erk, hedgehog and other signaling cascades, in skeletal development. The goal of this study was to investigate the in vivo role of Ptpn11 in postnatal root formation using loss-of-function approaches.
Methods: The Ptpn11^f/f mice were crossed with Prx1-Cre, which is expressed in the early limb bud mesenchyme as well as the subset of craniofacial mesenchyme (including odontoblasts). Conditional SHP2 knockout (cKO) mice were collected at days 2.5 and 7.5 postnatally. The combined approaches of micro-CT, x-ray, histology, and immunohistochemistry methods were used to characterize the dentin mineralization and tooth phenotypes.
Results: Studies of SHP2 cKO mice revealed no apparent changes in the crown dentin tubules and dentin matrix in both incisors and molars at postnatal day 2.5 and 7.5. However, there were no 3^rd molars and no molar root formation in SHP2 cKO group at the age of P7.5. Similarly, SHP2 cKO incisor root-analog was sharply reduced. The immunohistochemistry data revealed great reductions in Osx and BSP in SHP2 cKO odontoblasts. Interestingly, there was no apparent change in Col1a1. Taken together, a “root-less” phenotype in SHP2 cKO mice points to a novel function of SHP2 in the control of tooth root but not crown dentin formation.
Conclusions: Ptpn11 (SHP2) is essential for postnatal tooth root formation in both incisors and molars.