Collagen fibers provide guidance cues for capillary regrowth during regenerative angiogenesis in zebrafish

Abstract

Although well investigated, the importance of collagen fibers in supporting angiogenesis is not well understood. In this study, we demonstrate that extracellular collagen fibers provide guidance cues for endothelial cell migration during regenerative angiogenesis in the caudal zebrafish fin. Inhibition of collagen cross-linking by β-Aminopropionitrile results in a 70% shorter regeneration area with 50% reduced vessel growth and disintegrated collagen fibers. The disrupted collagen scaffold impedes endothelial cell migration and induces formation of abnormal angioma-like blood vessels. Treatment of the Fli//colRN zebrafish line with the prodrug Nifurpirinol, which selectively damages the active collagen-producing 1α2 cells, reduced the regeneration area and vascular growth by 50% with wider, but less inter-connected, capillary segments. The regenerated area contained larger vessels partially covered by endothelial cells embedded in atypical extracellular matrix containing cell debris and apoptotic bodies, macrophages and granulocytes. Similar experiments performed in early embryonic zebrafish suggested that collagens are important also during embryonic angiogenesis. In vitro assays revealed that collagen I allows for the most efficient endothelial cell migration, followed by collagen IV relative to the complete absence of exogenous matrix support. Our data demonstrates severe vascular defects and restricted fin regeneration when collagens are impaired. Collagen I therefore, provides support and guidance for endothelial cell migration while collagen IV is responsible for proper lumen formation and vascular integrity.

Anomalous diffusion and asymmetric tempering memory in neutrophil chemotaxis

“…It is characterized by rays that are aligned in parallel towards the the tip of the tail fin. This also applies to collagen fibers of the extracellular matrix and blood vessels [ 38 ]. Thus, these structural cues are in parallel to the direction of the chemotactic gradient which is generated by tail transection.…”

Spatial-temporal order-disorder transition in angiogenic NOTCH signaling controls cell fate specification

“…We focused on the extracellular matrix as a possible medium accounting for the positive and negative pattern-setting interactions. Indeed recently, it has been observed that collagen can be re-organized by the growing sprouts, so that it is concentrated around the extending sprouts and depleted elsewhere (19)(20)(21). We explored whether a similar distribution is also be observed for fibronectin, an ECM component that may be consequential to the angiogenesis processes.…”

Angiogenesis precedes myogenesis during regeneration following biopsy injury in skeletal muscle

“…The ECM aids in cell adhesion, cell-to-cell communication, and differentiation (28, 45). In addition to providing matrix structure, collagen fibers guide the growth of capillaries during regeneration (46). In such manner, the microenvironment of the provisional matrix established by FAPs and immune cells serves as the foundation for the regeneration of intact skeletal muscle (25).…”

“…Such ambiguity may be attributed to the persistence of basal laminae following efferocytosis, an outcome that prevails in established models (1, 4, 5, 11, 27). Preexisting basal laminae can provide guidance during regeneration of microvessels and myofibers (28–31, 46, 47), but a biopsy punch removes the entire tissue. A key finding here is that, in contrast to the concomitant regeneration of microvessels and myofibers discussed above, the onset of microvascular growth into the wound and perfusion across the wound precedes that of myofibers by approximately 1 week.…”