Abstract:Impaired cell polarity is a hallmark of diseased tissue. In the cardiovascular system, laminar blood flow induces endothelial planar cell polarity, represented by elongated cell shape and asymmetric distribution of intracellular organelles along the axis of blood flow. Disrupted endothelial planar polarity is considered to be pro-inflammatory, suggesting that the establishment of endothelial polarity elicits an anti-inflammatory response. However, a causative relationship between polarity and inflammatory resp… Show more
“…Similarly, no apicobasal polarity defects have been reported for par3 mutant follicular epithelial cells in Drosophila ( Shahab et al, 2015 ). Also, apicobasal polarity markers did not change in retinal endothelial cells of par3 knockout mice ( Hikita et al, 2018 ). Thus, the requirement of Par3 for apicobasal polarity may depend on developmental context and cell type.…”
Vertebrate neural tube formation depends on the coordinated orientation of cells in the tissue known as planar cell polarity (PCP). In the Xenopus neural plate, PCP is marked by the enrichment of the conserved proteins Prickle3 and Vangl2 at anterior cell boundaries. Here we show that the apical determinant Par3 is also planar polarized in the neuroepithelium, suggesting a role for Par3 in PCP. Consistent with this hypothesis, interference with Par3 activity inhibited asymmetric distribution of PCP junctional complexes and caused neural tube defects. Importantly, Par3 physically associated with Prickle3 and promoted its apical localization, whereas overexpression of a Prickle3-binding Par3 fragment disrupted PCP in the neural plate. We also adapted proximity biotinylation assay for use in Xenopus embryos and show that Par3 functions by enhancing the formation of the anterior apical PCP complex. These findings describe a mechanistic link between the apical localization of PCP components and morphogenetic movements underlying neurulation.
“…Similarly, no apicobasal polarity defects have been reported for par3 mutant follicular epithelial cells in Drosophila ( Shahab et al, 2015 ). Also, apicobasal polarity markers did not change in retinal endothelial cells of par3 knockout mice ( Hikita et al, 2018 ). Thus, the requirement of Par3 for apicobasal polarity may depend on developmental context and cell type.…”
Vertebrate neural tube formation depends on the coordinated orientation of cells in the tissue known as planar cell polarity (PCP). In the Xenopus neural plate, PCP is marked by the enrichment of the conserved proteins Prickle3 and Vangl2 at anterior cell boundaries. Here we show that the apical determinant Par3 is also planar polarized in the neuroepithelium, suggesting a role for Par3 in PCP. Consistent with this hypothesis, interference with Par3 activity inhibited asymmetric distribution of PCP junctional complexes and caused neural tube defects. Importantly, Par3 physically associated with Prickle3 and promoted its apical localization, whereas overexpression of a Prickle3-binding Par3 fragment disrupted PCP in the neural plate. We also adapted proximity biotinylation assay for use in Xenopus embryos and show that Par3 functions by enhancing the formation of the anterior apical PCP complex. These findings describe a mechanistic link between the apical localization of PCP components and morphogenetic movements underlying neurulation.
“…2). Moreover, EC polarization against the flow was also shown to be affected in low-flow vessels upon PAR3 loss (122). Cellular contractility is also essential for vascular patterning.…”
Section: Cell Migration In Vascular Patterningmentioning
confidence: 97%
“…2 ). Moreover, EC polarization against the flow was also shown to be affected in low-flow vessels upon PAR3 loss ( 122 ). Figure 2 Vascular patterning depends on blood flow and directional migration.…”
Section: Cell Migration In Vascular Patterningmentioning
The vascular system is a hierarchically organized network of blood vessels that play crucial roles in embryogenesis, homeostasis and disease. Blood vessels are built by endothelial cells - the cells lining the interior of blood vessels, through a process named vascular morphogenesis. Endothelial cells react to different biomechanical signals in their environment by adjusting their behavior: a) invade, proliferate and fuse to form new vessels (angiogenesis); b) remodel, regress and establish hierarchy in the network (patterning); c) maintain network stability (quiescence). Each step involves the coordination of endothelial cell differentiation, proliferation, polarity, migration, rearrangements and shape changes to ensure network integrity and an efficient barrier between blood and tissues. In this review, we highlighted the relevance and the mechanisms involving endothelial cell migration during different steps of vascular morphogenesis. We further present evidence on how impaired endothelial cell dynamics can contribute to pathology.
“…The cellular effects of thrombin are mediated in part by the G protein-coupled receptor family protease-activated receptors (PARs, include PAR1~4) [ 94 ]. The role of PARs in the progression of atherosclerosis has been confirmed [ 95 , 96 , 97 , 98 , 99 ], but the link between platelet-derived PARs and the actual pathogenesis of AS is less clear. Interestingly, while human platelets utilize two thrombin receptors, PAR-1 and PAR-4, mouse platelets utilize PAR-3 and PAR-4 [ 100 ].…”
Section: Platelet Receptors In Atherogenesismentioning
Besides their role in hemostasis and thrombosis, it has become increasingly clear that platelets are also involved in many other pathological processes of the vascular system, such as atherosclerotic plaque formation. Atherosclerosis is a chronic vascular inflammatory disease, which preferentially develops at sites under disturbed blood flow with low speeds and chaotic directions. Hyperglycemia, hyperlipidemia, and hypertension are all risk factors for atherosclerosis. When the vascular microenvironment changes, platelets can respond quickly to interact with endothelial cells and leukocytes, participating in atherosclerosis. This review discusses the important roles of platelets in the plaque formation under pro-atherogenic factors. Specifically, we discussed the platelet behaviors under disturbed flow, hyperglycemia, and hyperlipidemia conditions. We also summarized the molecular mechanisms involved in vascular inflammation during atherogenesis based on platelet receptors and secretion of inflammatory factors. Finally, we highlighted the studies of platelet migration in atherogenesis. In general, we elaborated an atherogenic role of platelets and the aspects that should be further studied in the future.
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