Borg5 is required for angiogenesis by regulating persistent directional migration of the cardiac microvascular endothelial cells.
The microvasculature is important for vertebrate organ development and homeostasis. However, the molecular mechanism of microvascular angiogenesis remains incompletely understood. Through studying Borg5 (Binder of the Rho GTPase 5), which belongs to a family of poorly understood effector proteins of the Cdc42 GTPase, we uncover a role for Borg5 in microvascular angiogenesis. Deletion of Borg5 in mice results in defects in retinal and cardiac microvasculature as well as heart development. Borg5 promotes angiogenesis by regulating persistent directional migration of the endothelial cells (ECs). In primary mouse cardiac ECs (MCECs), Borg5 associates with septins in the perinuclear region and colocalizes with actomyosin fibers. Both Borg5 deletion and septin 7 knockdown lead to a disruption of the perinuclear actomyosin and persistent directional migration. Our findings suggest that Borg5 and septin cytoskeleton spatially control actomyosin activity to ensure persistent directional migration of MCECs and efficient microvascular angiogenesis. Our studies reported here should offer a new avenue to further investigate the functions of Borg5, septin, and actomyosin in the microvasculature in the context of development and disease.
Department of Embryology, Carnegie Institution for Science, Baltimore, MD 21218 iPSC and Genome Engineering Core, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892.
Zhonghua
Z
Liu
Queenie P
QP
Vong
Chengyu
C
Liu
Yixian
Y
Zheng
D000205:Actomyosin / Q000235:genetics / Q000378:metabolism; D000818:Animals; D002465:Cell Movement; D003331:Coronary Vessels / Q000166:cytology* / Q000254:growth & development / Q000378:metabolism; D003598:Cytoskeletal Proteins; D042783:Endothelial Cells / Q000166:cytology* / Q000378:metabolism; D004730:Endothelium, Vascular / Q000166:cytology* / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D051379:Mice; D009206:Myocardium / Q000166:cytology* / Q000378:metabolism; D009389:Neovascularization, Pathologic; D018919:Neovascularization, Physiologic; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D012160:Retina / Q000166:cytology / Q000378:metabolism; D058112:Septins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D020741:rho GTP-Binding Proteins / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism
D003598:Cytoskeletal Proteins; D034741:RNA, Small Interfering; D000205:Actomyosin; C512895:Sept7 protein, mouse; D058112:Septins; C551798:Cdc42ep1 protein, mouse; D020741:rho GTP-Binding Proteins