The cellular mechanisms and molecular evolution of mammalian gliding membrane outgrowth - PROJECT SUMMARY/ABSTRACT During embryonic development, biochemical and mechanical signals generate highly coordinated patterns of gene expression and cellular behaviors. When these patterns are disrupted, they lead to developmental defects, which are a significant public health burden. Research into the developmental processes that are disrupted to cause developmental defects has traditionally been limited to a small number of model species. Interestingly, however, heritable disruptions to these processes can also give rise to morphological diversity over evolutionary timescales. Given the deep connection between deleterious and viable developmental variation, studying the mechanisms by which natural morphological diversity is generated can provide new insights into fundamental cellular and genetic processes that govern our own development. We study the development and evolution of a morphological adaptation, the lateral gliding membrane or patagium, using the sugar glider (Petaurus breviceps) as a model system. We have previously found that outgrowth of the sugar glider patagium is characterized by increased cell density in the mesenchyme and increased thickening in the epidermis, but the cellular behaviors and cell type-specific gene regulatory networks (GRNs) that mechanically induce this outgrowth, as well as the molecular basis of dermis-epidermis crosstalk in the developing patagium, are poorly understood. In Aim 1, using a combination of mathematical modeling, in vitro cell migration assays and skin explant experiments, and in vivo transgenesis experiments, I will investigate the role of cell migration and epidermal thickening in driving patagium outgrowth. Additionally, we have previously found that the key developmental ligands Wnt5a and Fgf7 are upregulated in the lateral patagia of both bats and sugar gliders, but the regulatory mechanisms by which these genes are activated in the lateral skin of both sugar gliders and bats remain unknown. In Aim 2, using a combination of epigenomic approaches, comparative genomic analyses, and Massively Parallel Reporter Assays (MPRAs), I will investigate the regulatory evolution of this trait in mammals with lateral patagia. Altogether, by studying a novel mammalian morphological structure using integrative mechanical, cell biological, and gene-regulatory approaches, this work will shed new light on how mammals sculpt and shape mesenchyme and skin during development in order to evolve novel tissue outgrowths. Under the supervision of my co-sponsors, I will 1) gain valuable experience in integrative developmental biology, 2) continue honing my skills as a quantitative, computational, and molecular biologist, and 3) gain teaching and outreach experience, and build the career skills necessary for my ultimate career goal of becoming a professor and principal investigator.
