Assessing Gene Expression Patterns in Mouse Models to Test Hypotheses About Human Head Evolution

Continuous fossil discoveries and recent analysis of genomic data are revealing that anatomically modern traits evolved following a complex evolutionary path. Our current understanding human evolution considers the skull likely as mosaic correlated whose development is in turn integrated with other organs, such brain. However, we still know little about complexity genetic networks supervising these processes developmental mechanisms underlying observed patterns morphological evolution. To further understand brain, it crucial to characterize gene expression provide detailed instructions organize cell behavior, tissue growth, organ patterning investigate how translates variation into phenotypic variation. We propose biology analyses using mouse models can enable experimental test hypotheses craniofacial diversification occurred across lineage. Here, combine molecular (Whole-Mount situ Hybridization), 3D imaging (Optical Projection Tomography), morphometric techniques assess changes space, time, intensity during embryonic development. used Fgfr2+/P253R Apert syndrome models, which an Fgfr2 mutation associated midfacial hypoplasia, brachycephaly, macrocephaly. These pathological phenotypes practical model similar those involved large globular braincase small, retracted face humans. compared two downstream targets Fgfr2, Dusp6 Hand2, relevant for brain development, 25 mice carrying 27 littermates collected between E10.5 E11.5. Qualitative comparisons revealed both genes co-expressed variable depending on time genotype. Results suggest FGF signaling pathway participates morphogenesis location timing induce systems. This supports hypothesis facial retraction encephalization direct responses common pathways. testing high throughput methods produce objective quantifications be future reveal genotype-phenotype correspondence traits.