The pattern of blood flow has long been thought to play a significant role in vascular morphogenesis, yet the flow-sensing mechanism that is involved at early embryonic stages, when flow forces are low, remains unclear. It has been proposed that endothelial cells use primary cilia to sense flow, but this has never been tested in vivo. Here we show, by noninvasive, high-resolution imaging of live zebrafish embryos, that endothelial cilia progressively deflect at the onset of blood flow and that the deflection angle correlates with calcium levels in endothelial cells. We demonstrate that alterations in shear stress, ciliogenesis, or expression of the calcium channel PKD2 impair the endothelial calcium level and both increase and perturb vascular morphogenesis. Altogether, these results demonstrate that endothelial cilia constitute a highly sensitive structure that permits the detection of low shear forces during vascular morphogenesis.
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| http://dx.doi.org/10.1016/j.celrep.2014.01.032 | DOI Listing |
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- Previous research indicated a connection between altered cerebral blood flow (CBF) after severe traumatic brain injury (sTBI) and poor executive function, but the effects on endothelial cells (ECs) and their cilia were not understood.
- A mouse model of sTBI was used to study changes in CBF, gene expression, and ciliary function in brain ECs through techniques like single cell RNA sequencing.
- Findings revealed sustained drops in CBF, alterations in EC sub-clusters, early activation of ischemic pathways, and a significant loss of ciliary gene expression and the cilia protein ARL13B in ECs within the first day post-injury, which continued throughout the injury period.
A New Method for Lateral Visualization of the Primary Cilia on the Surfaces of Cells Cultured on White Glass Rods.
Transl Vis Sci Technol
November 2024
Department of Ophthalmology, Kyoto Prefectural University of Medicine, Kyoto, Japan.
Purpose: To investigate the motility of the primary cilia of corneal endothelial cells (CECs), which exist like a hair on the cell surface, using our new in vitro method.
Methods: A white glass rod was heated with a gas burner to produce a rod approximately 0.5 mm in diameter and 20 mm in length and then coated with collagen.
Cell type mapping reveals tissue niches and interactions in subcortical multiple sclerosis lesions.
Nat Neurosci
December 2024
Department of Neurology, Division of Neuroimmunology, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system. Inflammation is gradually compartmentalized and restricted to specific tissue niches such as the lesion rim. However, the precise cell type composition of such niches, their interactions and changes between chronic active and inactive stages are incompletely understood.
View Article and Find Full Text PDFSpatiotemporal dynamics of primary and motile cilia throughout lung development.
bioRxiv
October 2024
Department of Molecular Biology, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, Texas, USA 75390.
Cilia are specialized structures found on a variety of mammalian cells, with variable roles in the transduction of mechanical and biological signals (by primary cilia, PC), as well as the generation of fluid flow (by motile cilia). Their critical role in the establishment of a left-right axis in early development is well described, as is the innate immune function of multiciliated upper airway epithelium. By contrast, the dynamics of ciliary status during organogenesis and postnatal development is largely unknown.
View Article and Find Full Text PDFLipid droplets sequester palmitic acid to disrupt endothelial ciliation and exacerbate atherosclerosis in male mice.
Nat Commun
September 2024
Department of Cell Biology, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, 250012, Jinan, China.
Disruption of ciliary homeostasis in vascular endothelial cells has been implicated in the development of atherosclerosis. However, the molecular basis for the regulation of endothelial cilia during atherosclerosis remains poorly understood. Herein, we provide evidence in male mice that the accumulation of lipid droplets in vascular endothelial cells induces ciliary loss and contributes to atherosclerosis.
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