Phosphorylation of ERK and MEK in the laCL of mouse models with dysregulated RTK signaling. Compared with control (A, B), pERK and pMEK staining was similar in the Fgf3−/− mutant mouse laCL (C, D). In the Fgf3−/−;Fgf10+/− mouse, the levels of ERK and MEK phosphorylation were greatly reduced, and the laCL was small and malformed (E, F). While deletion of Spry4−/− did not noticeably affect pERK and pMEK staining (G, H) compared with control, the Spry2+/−;Spry4−/− mutant showed increased levels of ERK and MEK phosphorylation in the DESC compartment (SR and OEE) as marked by green arrows (I, J). In the BrafL597V gain-of-function mutation (Braf GOF) mouse, pERK staining was increased in the T-A and DESC regions as marked by white and green arrows, respectively, (K) while pMEK staining did not differ significantly (L) compared with control. In HrasG12V gain-of-function mutation (Hras GOF) mutants, phosphorylation of MEK and ERK was increased in the T-A (white arrowhead) and OEE (green arrowhead) regions (M, N) compared with control. pERK staining was also increased in the pre-am region (blue arrowhead; M). DESC, dental epithelial stem cell; laCL, labial cervical loop; OEE, outer enamel epithelium; pre-am, preameloblast; SR, stellate reticulum; T-A, transit-amplifying.