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J. L. Walker, N. Zhai, L. Zhang, I. Wolff, B. M. Bleaken, A. S. Menko; Leaders and Followers: Wound Healing in a PCO Model. Invest. Ophthalmol. Vis. Sci. 2010;51(13):2632.
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© ARVO (1962-2015); The Authors (2016-present)
An essential element of epithelial sheet wound healing is the regulated migration of the epithelial cells into the wound area. We examined the mechanisms that drive and regulate collective cell migration during tissue repair in the lens using a unique ex vivo wound healing model originally developed to study PCO, where cell response to injury is studied in a native microenvironment. These studies focused on the distinct functions of leader and follower cells in wound repair.
Mock cataract surgery in chick embryo lenses created a highly reproducible wound area. Properties of leader and follower cells in the wound healing model were analyzed by confocal microscopy following immunostaining.
Following mock cataract surgery a distinct subpopulation of vimentin-rich cells that were associated with the anterior aspects of the lens epithelium quickly migrated to the wound edge where they exhibited properties of leader cells that guide the repair of epithelia. These mesenchymal cells lacked cortical ZO-1. Some leader cells had protrusions oriented in the direction of migration while other leader cells were oriented perpendicular to the wound edge with actin filaments organized as a purse string. The protrusions of the leader cells had few actin filaments but were rich in vimentin filaments linked to paxillin-containing focal adhesions. The lens epithelial cells were the follower cells, moving forward as a collective sheet that maintained close ZO-1-rich apical cell-cell junctions but had remodeled their N-cadherin cell-cell junctions. In the dynamically moving follower cells situated just behind the leader cell population N-cadherin junctions were present in overlapping intermembranous networks while cortactin and actin were found in cryptic lamellipodia polarized toward the wound edge.
The wounded lens epithelium behaves as follower cells with cryptic cortactin/actin-rich lamellipodia likely responsible for forward movement of the epithelium. These epithelial cells are led by a subpopulation of vimentin-rich mesenchymal cells whose rapid migration to the wound edge suggests a central role as regulators of the wound-healing process.
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