Exogenous FGF8 signaling in osteocytes leads to mandibular hypoplasia in mice

Objective Fibroblast growth factor 8 (FGF8) signaling is essential in regulating craniofacial osteogenesis. This study aims to explore the effect of altered FGF8 signaling in maxillomandibular development during embryogenesis. Materials and Methods Dmp1(Cre);R26R(mTmG) mice were generated to trace Dmp1(+) cell lineage, and Dmp1(Cre);R26R(Fgf8) mice were generated to explore the effects of augmented FGF8 signaling in Dmp1(+) cells on osteogenesis with a focus on maxillomandibular development during embryogenesis, as assessed by whole mount skeletal staining, histology, and immunostaining. Additionally, cell proliferation rate and the expression of osteogenic genes were examined. Results Osteocytes of maxillomandibular bones were found Dmp1-positive prenatally, and Fgf8 over-expression in Dmp1(+) cells led to mandibular hypoplasia. While Dmp1(Cre) allele functions in the osteocytes of the developing mandibular bone at as early as E13.5, and enhanced cell proliferation rate is observed in the bone forming region of the mandible in Dmp1(Cre);R26R(Fgf8) mice at E14.5, histological examination showed that osteogenesis was initially impacted at E15.5, along with an inhibition of osteogenic differentiation markers. Conclusions Augmented FGF8 signaling in Dmp1(+) cells lead to osteogenic deficiency in the mandibular bones, resulting in mandibular hypoplasia.