Pten

**Abstract(s):** **(1) Inactivation of Pten in osteo-chondroprogenitor cells leads to epiphyseal growth plate abnormalities and skeletal overgrowth:** To study the role of the Pten tumor suppressor in skeletogenesis, Ford-Hutchinson et al. (2007) generated mice lacking this key phosphatidylinositol 3'-kinase pathway regulator in their osteo-chondroprogenitors. A phenotype of growth plate dysfunction and skeletal overgrowth was observed. **(2) Mind the gap -- genetic manipulation of basicranial growth within synchondroses modulates calvarial and facial shape in mice through epigenetic interactions:** 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, Parsons et al. (2015) 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, the authors 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. **(3) Mouse models and the evolutionary developmental biology of the skull:** Understanding development is relevant to understanding evolution because developmental processes structure the expression of phenotypic variation upon which natural selection acts. Advances in developmental biology are fueling a new synthesis of developmental and evolutionary biology, but it remains unclear how to use developmental information that largely derives from a few model organisms to test hypotheses about the evolutionary developmental biology of taxa such as humans and other primates that have not been or are not amenable to direct study through experimental developmental biology. In this article, Hallgrimsson et al. (2008) discuss how and when model organisms like mice are useful for studying the evolutionary developmental biology of even rather distantly related and morphologically different groups like primates. A productive approach is to focus on processes that are likely to play key roles in producing evolutionarily significant phenotypic variation across a large phylogenetic range. The authors illustrate this approach by applying the analysis of craniofacial variation in mouse mutant models to primate and human evolution.