Embryonic inhibition of colony‐stimulating factor 1 receptor impacts craniofacial morphogenesis

Abstract

AbstractObjectivesColony‐stimulating factor‐1 receptor (CSF1R) is vital for the recruitment of monocytes, and their proliferation and differentiation into functional osteoclasts. Mouse studies, where CSF1R and its cognate ligand are absent, have significant craniofacial phenotypes, but these have not been studied in detail.Materials and MethodsPregnant CD1 mice were fed diets laced with CSF1R inhibitor—PLX5622 starting at embryonic day 3.5 (E3.5) up to birth. Pups were collected at E18.5 to study CSF1R expression using immunofluorescence. Additional pups were studied at postnatal day 21 (P21) and P28 using microcomputed tomography (μCT) and Geometric Morphometrics, to evaluate craniofacial form.ResultsCSF1R‐positive cells were present throughout the developing craniofacial region, including the jaw bones, surrounding teeth, tongue, nasal cavities, brain, cranial vault and base regions. Animals exposed to the CSF1R inhibitor in utero had severe depletion of CSF1R‐positive cells at E18.5 and had significant differences in craniofacial form (size and shape) at postnatal timepoints. Centroid sizes for the mandibular and cranio‐maxillary regions were significantly smaller in CSF1R‐inhibited animals. Proportionally, these animals had a domed skull, with taller and wider cranial vaults and shortening of their midfacial regions. Mandibles were smaller vertically and anterio‐posteriorly, with proportionally wider inter‐condylar distances.ConclusionsEmbryonic inhibition of CSF1R impacts postnatal craniofacial morphogenesis, with significant influences on the mandibular and cranioskeletal size and shape. These data indicate that CSF1R plays a role in early cranio‐skeletal patterning, likely through osteoclast depletion.