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TRANSCRIPTIONAL REGULATION OF BONE FORMATION, MECHANOSENSING, AND EVOLUTION

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Abstract
Given that bone remodeling is a dynamic process, the output of which is dependent upon time, levels of mechanical input, and the ability of bones to respond to that mechanical stimulus, I assessed regulation of gene expression in the craniofacial region to determine how a response happens during mechanosensing and bone remodeling. To do this, I used African cichlids as a model, as they known for their rapid speciation rates, high phenotypic variation within and between species, and ability to remodel their bones in response to mechanical loading. In chapter 2, I combined RNA-seq and ATAC-seq datasets to determine with high confidence genes are responsible for plasticity and shape differences in cichlid species with different feeding morphologies. In particular, I found genes that were both differentially expressed and differentially accessible to transcriptional machinery that were implicated in cell cycle progression. In chapter 3, using qPCR, I was able to determine that time is a critical factor in assessing plasticity and the response of certain species to mechanical input. This was paired with 2D morphometrics for shape analysis over time to show that species that do not fall on the extreme end of phenotypic variation are more genetically plastic, and gives insights into the underpinnings of evolution in cichlid jaw morphology. Results from both chapters 2 and 3 suggested that certain environments facilitate larger changes in gene expression than others. In chapter 4, using molecular techniques such as qPCR coupled with enzymatic staining, I found that when mechanosensitive structures in the cell are ablated, gene expression regulation collapses over time, and specific sites of bone remodeling activity are less predictive. Taken together, this body of work supports previous research in the field and gives insight into the regulation of gene expression during bone remodeling, plasticity, and evolution.
Type
dissertation
Date
2023-09
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