Genetic and developmental mechanisms that underlie craniofacial (co)variation

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Abstract/Summary: The vertebrate craniofacial skeleton is a dynamic organ that arises and is maintained through an intricate balance of genetic and environmental inputs. Disruptions to either can lead to deleterious health outcomes. While significant progress has been made toward understanding the genetic and cellular mechanisms that underlie early craniofacial patterning, much less is known about the basis for craniofacial variation that manifests over extended periods of development, and depends upon the environmental context in which it occurs. Whether it's the physical interactions between cells and tissues within the developing embryo, or the mechanic forces imposed on the system, these contexts will determine how genetically-encoded systems unfold over time to determine craniofacial geometry. Implicit to these ideas is feedback in the system. Feedback is how disparate developmental units come together to form integrated functional systems - e.g., reciprocal signaling between adjacent but developmentally distinct tissues. It is also necessary for normal growth and homeostasis in kinetic systems - e.g., progenitor cells must sense environmental inputs, including mechanical load, and adjust developmental processes accordingly. Broadly speaking this proposal seeks to understand how both types of feedback are regulated at the genetic level. In doing so, three specific questions will be addressed: (1) What are the genes that contribute to craniofacial shape? (2) Do they exert their effects on more than one tissue, either via pleiotropy or as part of the same signaling pathway? (3) How do these loci interact with the environment, via mechanosensing, to affect variation in facial form? Cichlid fishes will be used as the experimental model, as they have undergone extensive evolutionary modifications of their skulls and jaws in a very brief period of time, making them ideal for genetic/genomic mapping. Cichlids are also well known for their capacity to remodel their jaws under different foraging environment, but not all cichlids share this ability, and thus plasticity itself is genetically determined and has diverged in this system. Cichlids therefore represent an ideal model to identify and parse the genetic, environmental, and GxE effects that underlie craniofacial variability. This proposal leverages these experimental attributes, and integrates advanced phenotypic, genotypic and functional tools to provide a more holistic understanding of the mechanisms that underlie craniofacial shape.