Conditional and full mutants of Apert Syndrome FGFR2 S252W

Background: Major cell-to-cell signaling pathways, such as the fibroblast growth factors and their four receptors (FGF/FGFR), are conserved across a variety of animal forms. FGF/FGFRs are necessary to produce several “vertebrate-specific” structures, including the vertebrate head. Here, we examine the effects of the FGFR2 S252W mutation associated with Apert syndrome on patterns of cranial integration. Our data comprise micro-computed tomography images of newborn mouse skulls, bred to express the Fgfr2 S252W mutation exclusively in either neural crest or mesoderm-derived tissues, and mice that express the Fgfr2 S252W mutation ubiquitously. Results: Procrustes-based methods and partial least squares analysis were used to analyze craniofacial integration patterns. We found that deviations in the direction and degree of integrated shape change across the mouse models used in our study were potentially driven by the modular variation generated by differing expression of the Fgfr2 mutation in cranial tissues. Conclusions: Our results demonstrate that covariation patterns can be biased by the spatial distribution and magnitude of covariation produced by underlying developmental-genetic mechanisms that often impact the phenotype in disproportionate ways. In craniosynostosis, understanding how localized aberrant signaling alters how different parts of the skull grow and integrate can serve as a therapeutic guide for surgical interventions.