Avian species display a remarkable diversity of facial morphologies, from the small, pointed, insect-catching beak of the common sparrow, to the long, narrow, nectar-sipping beak of a hummingbird. Using fate-mapping studies, we know that all facial skeletal elements are derived from neural crest mesenchyme (NCM), a multipotent embryonic cell population. From transplant experiments, we know that NCM plays an instructive role in patterning and growth in the face (i.e., when we transplant quail NCM into a duck host, the chimera forms a quail-like face and beak). What remains to be understood is how NCM carries out the components of what is undoubtedly a very complex task - to pattern beaks with great precision for function in established niches, but also to allow plasticity for evolution in response to changes in the natural environment.
Thus, one of the questions I address during my dissertation research is what are developmental, cellular, and molecular mechanisms underlying evolvability in avian faces? I have previously been intrigued by the rapid rate of generation of novel beak morphologies as historically described in Darwin's finches and other models. To begin to understand these phenomena, I investigated the function, regulation, and evolution of one transcription factor, Runx2, as a model for understanding processes that can modulate the generation of heritable, selectable, phenotypic variation.
Runx2 is often considered a master regulator of osteogenesis. However, mechanisms by which Runx2 might regulate timing of osteogenesis in vivo have not been previously described. Here, by using a unique avian chimeric experimental system, we identify Runx2 as a critical player in both NCM-dependent timing of osteogenesis and developmental growth and patterning of the craniofacial complex. Specifically, we find that NCM controls stage- and species-specific cell cycle progression and Runx2 expression in highly interwoven processes. Further, Runx2 expression levels affect mandible size and correlate to species-specific sequence variation at a highly evolvable Runx2 regulatory region. Taken together, these data suggest that NCM may be able generate a range of skeletal element sizes and morphologies in part by temporally regulating cell cycle in conjunction with cell differentiation through highly regulated, mutation-labile transcription factors such as Runx2.