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Epithelial Morphogenesis
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overview
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My lab takes an integrative approach to studying organ morphogenesis. We are currently probing how cells migrate collectively & how basement membrane ECMs are assembled.
Collective cell migration - The collective migration of cells within an epithelial sheet underlies tissue remodeling events associated with morphogenesis, wound repair, and the spread of many cancers. Yet little is known about how each epithelial cell coordinates its individual migratory behaviors with those of its neighbors, or how epithelial motility shapes tissues during development. We recently discovered a novel planar signaling system that coordinates leading and trailing edge dynamics between neighboring epithelial cells, and are now working to elucidate the mechanistic basis of this signaling. We are also investigating how collective cell migration can be harnesses to create a stable, planar tissue pattern within an epithelium for subsequent morphogenesis.
Basement membrane dynamics – Basement membrane is a sheet-like extracellular matrix that lines the basal surface of all epithelial tissues. This complex protein network provides structural stability to the monolayer, promotes cell-cell and cell-matrix signaling, and acts as a physical barrier to metastasis. Despite their ubiquity and many essential functions, we know surprisingly little about how basement membranes are built or how they are remodeled during development. We are taking a comprehensive approach to identifying: the cellular mechanisms underlying basement membrane biosynthesis and secretion, how basement membrane biosynthetic programs are modulated to construct diverse matrix architectures, and how different basement membrane architectures ultimately influence organ morphogenesis.
Experimental system – We perform these studies in the Drosophila egg chamber, which is an organ-like structure in the ovary that will give rise to one egg. Each egg chamber is comprised of a germ cell cluster, surrounded by a somatic epithelium of follicle cells. The follicle cells produce their own basement membrane, which ensheaths the organ. Though initially spherical, egg chambers lengthen as they mature. This morphogenesis depends on a dramatic collective migration of the follicle cells across their basement membrane, which causes the entire egg chamber to rotate within its surrounding matrix. Importantly, the follicle cells also remodel the basement membrane as they crawl along its surface, creating a polarized array of fibrils in the direction of tissue movement. This fibrillar matrix is then thought to act as a “molecular corset” that resists the expansive growth of the germ cells to directionally bias egg chamber growth, and thus create the elongated shape of the egg. A major strength of this system is that the collective migration and basement membrane remodeling both occur on the egg chamber’s outer surface, which allows us to image dynamic cell behaviors - in a living organ - with exquisite clarity. Moreover, we can use the sophisticated genetic tools of Drosophila to identify the underlying molecular mechanisms. Please check out the papers below to see what we have already discovered!
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