Abstract
Angiogenesis and vascular remodeling are driven by extensive endothelial cell movements. Here, we present in vivo evidence that endothelial cell movements are associated with oscillating lamellipodia-like structures, which emerge from cell junctions in the direction of cell movements. High-resolution time-lapse imaging of these junction-based lamellipodia (JBL) shows dynamic and distinct deployment of junctional proteins, such as F-actin, VE-cadherin and ZO1, during JBL oscillations. Upon initiation, F-actin and VE-cadherin are broadly distributed within JBL, whereas ZO1 remains at cell junctions. Subsequently, a new junction is formed at the front of the JBL, which then merges with the proximal junction. Rac1 inhibition interferes with JBL oscillations and disrupts cell elongation—similar to a truncation in ve-cadherin preventing VE-cad/F-actin interaction. Taken together, our observations suggest an oscillating ratchet-like mechanism, which is used by endothelial cells to move over each other and thus provides the physical means for cell rearrangements.
Highlights
Angiogenesis and vascular remodeling are driven by extensive endothelial cell movements
We propose that the oscillating behavior of junction-based lamellipodia (JBL), which depends on F-actin polymerization as well as contractility, provides a general mechanism of endothelial cell movement during blood vessel formation and vascular remodeling
The dorsal longitudinal anastomotic vessel (DLAV) presents a welldefined in vivo model to analyze how a wide repertoire of endothelial cell activities leads to the formation of a new blood vessel, starting with establishment of an interendothelial contact point, followed by the formation of a continuous luminal surface and the transformation from a unicellular to a multicellular tubular architecture
Summary
Angiogenesis and vascular remodeling are driven by extensive endothelial cell movements. The cardiovascular system is one of the most ramified vertebrate organs and is characterized by an extraordinary plasticity It forms during early embryonic development, and it expands and remodels to adapt to the needs of the growing embryo. Blood vessel morphogenesis and remodeling are accomplished by endothelial cell behaviors including cell migration, cell rearrangement and cell shape changes[3,4,5]. This repertoire of dynamic behaviors allows endothelial cells to rapidly respond to different contextual cues, for example during angiogenic sprouting, anastomosis, diapedesis or regeneration. The observation that loss of VE-cad function can inhibit cell rearrangements suggests an active contribution to this process[12,13]
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