B2 or Not B2: Loss of ephrin-B2 in Endothelial Cells During Development, Homeostasis, and Regeneration

Monsanto Auditorium

Our developing understanding of skeletal muscle regeneration includes interactions between satellite cells and their progeny with other cell types including resident and infiltrating immune cells, FAPs, and endothelial cells. Ephrin-B2 is a cell surface molecule that is necessary for angiogenesis during development and is thought to act in capillary sprouting. In mice we show that endothelial cell specific conditional deletion of ephrin-B2 during development prior to e10.5 mimics the global knockout phenotype and results in embryonic death due to hemorrhage within 12- 24 hours of tamoxifen injection. In the adult, conditional deletion of ephrin-B2 during homeostasis has no deleterious effects. Following muscle injury with the myotoxin BaCl2, conditional deletion of ephrin-B2 does not prevent vascular regeneration, but the capillaries in ephrin-B2CKO mice show altered morphology after regeneration including extensive disorganization and decreased branching. Muscle regeneration in these animals also occurs but is delayed. We also asked whether pharmacological inhibition of VEGFR signaling by Axitinib, a competitive inhibitor, would prevent capillary regeneration and potentially affect muscle regeneration. Treatment with Axitinib during homeostasis had no deleterious effect, but treatment during muscle regeneration resulted in disorganization of the capillary network and reduced vessel density. Muscle regeneration in mice treated with Axitinib does not appear to be grossly impaired. Our data suggest that ephrin-B2 is only necessary during early embryogenesis prior to e10.5, and that inhibition of sprouting angiogenesis does not significantly impact muscle regeneration. 

Doctoral Program Committee

Dr. D Cornelison
Dr. Steven S. Segal
Dr. Elizabeth Bryda
Dr. Yves Chabu

Postdoctoral position: Dr. Alexandra Diller accepted a postdoctoral position with the BREATHE Training Program at the University of Florida-Gainsville. She is investigating hyperbaric oxygen treatment after SCI under the mentorship of Dr. David Fuller in the Department of Physical Therapy.

Speaker Information

Alexandra Diller
Ph.D. Candidate - Cornelison Lab
Division of Biological Sciences
University of Missouri