Planar Cell Polarity and
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Cilia and CiliogenesisHow do cilia form and control cell signaling during development?
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Systems Biology of DevelopmentHow can we apply large scale proteomic and genome approaches to specific vertebrate embryonic tissues?
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The captivating aspect of embryos is that they construct themselves. It is the behavior of the individual cells within that directs the construction of our tissues and organs. Defects in these behaviors are a key cause of human birth defects, which kill more than twice as many children as pediatric cancer. For the last two decades, our lab has used in vivo imaging, biomechanics, and proteomics to understand the collective cell behaviors known as convergent extension that elongate the body axis and close the neural tube in vertebrate embryos. Current work focuses on the nexus between tissue-specific developmental signaling systems that govern cell movements (e.g. Planar Cell Polarity and Nodal signaling) and the ubiquitous cell biological machinery that executes them (e.g. actomyosin contraction, and cadherin-based cell-cell adhesion).
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The emergence of the final, functional form of each specific cell type is a core problem in developmental biology. For over a decade, we have used multiciliated cells (MCCs) as a paradigm in which to explore cell-type diversification, from initial specification, through cellular morphogenesis, to function (in this case, polarized ciliary beating and the generation of patterned fluid flow). Along the way, we have defined new transcriptional circuits, identified a novel liquid-like organelle, and shed light on the molecular etiology of human motile ciliopathies. Current projects include mapping the interactome of motile cilia at amino acid resolution and revealing the mechanisms by which dynein motors are assembled and deployed to cilia.
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Over the last 15 years, the Wallingford Lab has maintained a stable of collaborators allowing us to use genomic and proteomic tools to accelerate our studies of developmental cell biology. From assembly of amphibian genomes, to high-content in vivo imaging, to tissue-specific affinity purification/mass-spec in embryos, this collaboration supports all projects in the Wallingford Lab. Recent work has focused on using evolutionary distant organisms and novel unbiased methods such as co-fractionation mass-spec and cross-linking mass-spec to map and explore protein interactomes.
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