Craniofacial abnormalities from TNAP and PHOSPHO1 deletion highlight their dual role in bone and tooth mineralisation

While tissue non-specific alkaline phosphatase (TNAP) and PHOSPHO1 are increasingly recognised as key cooperative regulators of postnatal skeletal mineralisation, the extent to which they interact during craniofacial morphogenesis has yet to be fully established. To elucidate these mechanisms, we generated mice harbouring a Prx1-mediated deletion of Alpl on a global Phospho1-null background, enabling a comprehensive assessment of phosphatase-mediated regulation of mineralisation across the developing craniofacial skeleton and dentoalveolar tissues. We show that whilst conditional deletion of Alpl had no effect on cranial and mandibular measurements, deletion of Phospho1 resulted in a craniofacial hypoplasia characterised by frontonasal hypoplasia, reduced cranial vault height, and mandibular micrognathia, alongside increased intersphenoidal synchondrosis volume. This craniofacial hypoplasia phenotype was exacerbated by the dual deletion of Alpl and Phospho1, which resulted in further decreases in dentin volume and thickness. Together, these data indicate that TNAP and PHOSPHO1 play key roles in both craniofacial and dental development and add further evidence towards their synergistic role in supporting permissive biomineralisation.