Processes and patterns: Insights on cranial covariation from an Apert syndrome mouse model

Nandini Singh, Yann Heuzé, Greg Holmes

Research output: Contribution to journalArticlepeer-review


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 overall results demonstrate that covariation patterns can be biased by the spatial distribution and magnitude of variation produced by underlying developmental-genetic mechanisms that often impact the phenotype in disproportionate ways.

Original languageEnglish
Pages (from-to)1684-1697
Number of pages14
JournalDevelopmental Dynamics
Issue number10
StatePublished - Oct 2022


  • Fgfr2 S252W
  • geometric morphometrics
  • modularity
  • morphological integration
  • partial-least squares


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