ABSTRACT
Recent fossil discoveries and genomic data have revolutionized our understanding of human evolution. Despite these breakthroughs, we still know little about the developmental mechanisms underlying patterns of morphological evolution. Here, we combine developmental biology tools and 3D imaging techniques (i.e., whole-mount in situ hybridization and optical projection tomography) with shape analysis to assess changes in the space, time, and intensity of gene expression patterns during embryonic development. To illustrate the method, we used Fgfr2+/P253R Apert syndrome mouse models in which an Fgfr2 mutation is associated with midfacial hypoplasia, brachycephaly, and macrocephaly. These pathological conditions could result from processes similar to those involved in the evolution of a large globular braincase and a small retracted face in modern humans. Expression patterns of two downstream targets of Fgfr2 relevant for cell processes driving both brain and craniofacial development, Dusp6 and Hand2, were compared in unaffected and mutant mice (E10.5–E11.5). Qualitative comparisons revealed that both genes are co-expressed in the brain and face with variable intensity depending on developmental time and genotype. Results suggest that the FGF signaling pathway participates in brain and face morphogenesis and that changes in the location and timing of gene expression can induce correlated changes in brain and craniofacial systems. This supports the hypothesis that facial retraction and encephalization likely evolved as direct and correlated responses to common signaling pathways. Further automatic throughput methods producing efficient quantifications of gene expression patterns will help disentangle complex genotype-phenotype correspondences and provide the means for testing hypotheses of human evolution.
