Anti-NES monoclonal antibody, clone TQ204

The platelet-derived growth factor receptor-alpha (PDGFR alpha) principally mediates growth factor signals in oligodendroglial progenitors and is involved in oligodendrogenesis and myelinogenesis in the developing spinal cord. However, the role of PDGFR alpha in the developing forebrain remains relatively unknown. We established a conditional knockout mouse for the Pdgfra gene (N-PR alpha-KO) using a Nestin promoter/enhancer-driven Cre recombinase and examined forebrain development. The expression of was efficiently suppressed in the Olig2(+) cells in N-PR alpha-KO mice. In these mice, Olig2(+) cells were slightly decreased during embryonic periods. The decrease was particularly striking during the postnatal period. The commitment of Pdgfra-inactivated Olig2(+) cells to Sox10(+) oligodendroglial-lineage was largely suppressed. Surviving Olig2(+) cells and Sox10(+) cells were distributed widely in the N-PR alpha-KO mouse brain, similarly to those in control mice until the early neonatal period. After that, these cells were drastically depleted in the forebrain during the second postnatal week. The brains of N-PR alpha-KO mice were severely hypomyelinated, and these mice died on approximately P17 with motor disturbances. Disturbed axonal fibers and extensively aberrant vascular formations appeared in the postnatal N-PR alpha-KO mouse brains. After the defective PDGFR alpha signal in the forebrain, these phenotypes were clearly different from those in the spinal cord that showed defective populations expansion and migration of oligodendroglial lineage and premature myelination, as previously described. In contrast, areas of severe hypomyelination were common to both anatomical sites. PDGFR alpha was critically involved in the myelination of the forebrain and may differently regulate oligodendroglial lineage between the forebrain and spinal cord. (C) 2020 IBRO. Published by Elsevier Ltd. All rights reserved.

Blood vessels are constantly exposed to shear stress, a biomechanical force generated by blood flow. Normal shear stress sensing and barrier function are crucial for vascular homeostasis and are controlled by adherens junctions (AJs). Here we show that AJs are stabilized by the shear stress-induced long non-coding RNA LASSIE (linc00520). Silencing of LASSIE in endothelial cells impairs cell survival, cell-cell contacts and cell alignment in the direction of flow. LASSIE associates with junction proteins (e.g. PECAM-1) and the intermediate filament protein nestin, as identified by RNA affinity purification. The AJs component VE-cadherin showed decreased stabilization, due to reduced interaction with nestin and the microtubule cytoskeleton in the absence of LASSIE. This study identifies LASSIE as link between nestin and VE-cadherin, and describes nestin as crucial component in the endothelial response to shear stress. Furthermore, this study indicates that LASSIE regulates barrier function by connecting AJs to the cytoskeleton. Stanicek et al identify a shear stress-induced long non-coding RNA they name LASSIE, which stabilises junctions between endothelial cells through interactions with junctional and cytoskeletal proteins. This study provides insights into how a transcript that does not encode a protein controls endothelial response to forces associated with blood flow and endothelial barrier function.