title: Mind the gap: genetic manipulation of basicranial growth within synchondroses modulates calvarial and facial shape in mice through epigenetic interactions.
abstract: Phenotypic integration patterns in the mammalian skull have long been a focus of intense interest as a result of their suspected influence on the trajectory of hominid evolution. Here we test the hypothesis that perturbation of cartilage growth, which directly affects only the chondrocranium during development, will produce coordinated shape changes in the adult calvarium and face regardless of mechanism. Using two murine models of cartilage undergrowth that target two very different mechanisms, we show that strong reduction in cartilage growth produces a short, wide, and more flexed cranial base. This in turn produces a short, wide face in both models. Cranial base and face are already correlated early in ontogeny, and the relationship between these modules gains structure through postnatal growth and development. These results provide further evidence that there exist physical interactions between developing parts of the phenotype that produce variation at a distance from the actual locus upon which a particular selective pressure is acting. Phenotypic changes observed over the course of evolution may not all require adaptationist explanations; rather, it is likely that a substantial portion of observed phenotypic variation over the history of a clade is not directly adaptive but rather a secondary consequence of some local response to selection.
authors.affiliation: McCaig Institute for Bone and Joint Health, University of Calgary, Calgary, Canada; Department of Cell Biology & Anatomy, Cumming School of Medicine, University of Calgary, Calgary, Canada.
authors.forename: Trish E
authors.initials: TE
authors.lastname: Parsons
authors.affiliation: McCaig Institute for Bone and Joint Health, University of Calgary, Calgary, Canada; Department of Biochemistry and Molecular Biology, Cumming School of Medicine, University of Calgary, Calgary, Canada.
authors.forename: Charlene M
authors.initials: CM
authors.lastname: Downey
authors.affiliation: McCaig Institute for Bone and Joint Health, University of Calgary, Calgary, Canada; Department of Biochemistry and Molecular Biology, Cumming School of Medicine, University of Calgary, Calgary, Canada.
authors.forename: Frank R
authors.initials: FR
authors.lastname: Jirik
authors.affiliation: McCaig Institute for Bone and Joint Health, University of Calgary, Calgary, Canada; Department of Cell Biology & Anatomy, Cumming School of Medicine, University of Calgary, Calgary, Canada.
authors.forename: Benedikt
authors.initials: B
authors.lastname: Hallgrimsson
authors.affiliation: McCaig Institute for Bone and Joint Health, University of Calgary, Calgary, Canada; Department of Cell Biology & Anatomy, Cumming School of Medicine, University of Calgary, Calgary, Canada.
authors.forename: Heather A
authors.initials: HA
authors.lastname: Jamniczky
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000033:anatomy & histology* / Q000254:growth & development / Q000378:metabolism; D024043:Collagen Type II / Q000235:genetics / Q000378:metabolism; D044127:Epigenesis, Genetic; D005145:Face / Q000033:anatomy & histology*; D051379:Mice; D008822:Mice, Transgenic; D051059:PTEN Phosphohydrolase / Q000235:genetics / Q000378:metabolism; D025341:Principal Component Analysis; D019291:Skull Base / Q000254:growth & development*
chemical_list: D024043:Collagen Type II; D051059:PTEN Phosphohydrolase