Apicobasal polarity of brain endothelial cells

Worzfeld, Thomas; Schwaninger, Markus

doi:10.1177/0271678x15608644

Cited by 74 publications

(59 citation statements)

References 208 publications

(294 reference statements)

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“…As we have already mentioned, LFCs placed at the outer spheroid layer exhibited signs of apical-basal polarity, such as the presence of apical microvilli and adherens junctions. Intercellular junctions play an essential role in maintaining apical-basal cell polarity since they serve as a physical limit between the apical/luminal and basolateral/luminal cell compartments [47]. Early cell-cell contacts during spheroid formation would induce the formation of intercellular junctions, which recruit and activate polarity proteins.…”

Section: Discussionmentioning

confidence: 99%

Structure and ultrastructure of neurospheres spontaneously generated in culture from sheep ovarian cortical cells.

Salvador¹,

Maldonado²,

Galicia³

et al. 2019

Preprint

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Background: Neurospheres derived from adult stem cells of non-neural tissues represent a promising source of neural stem cells (NSCs) and neural progenitor cells (NPCs) for autologous cell therapy in neurological diseases. Analyzing the fine structure of neurospheres can provide pivotal information regarding the phenotype of spheroid-integrating cells, being useful for cell characterization during differentiation, and oncogenic transformation. Neurospheres can be generated by culturing ovarian cortical cells under particular conditions. In order to assess the reliability of use of these spheroids in regenerative medicine, developmental biology, and to state whether they share morphological features with central nervous system (CNS) derived neurospheres, they were analyzed by light and transmission electron microscopy. Sheep ovarian cortical cells were cultured in serum-free medium for 21 days to generate neurospheres. On days 10, 15 and 21 of culture, expression of pluripotency (Nanog, Oct4, Sox2), and NSC/NPC (nestin, Pax6, P75NTR) transcripts by qRT-PCR, immunolocalization of NSC/NPC antigens (nestin, Pax6, P75NTR), structure, and ultrastructure, were analyzed in spheroids. Results: Spheroids expressed transcripts and antigens of pluripotency, and NSC/NPC. Structural analyses revealed that cells were arranged in a peripheral sheet cover comprised by a few layers of spindle-shaped cells exhibiting frequent mitoses, and large round cells; and an inner core, with intermediate-sized cells showing frequent events of apoptosis and necrosis. Ultrastructural analyses showed that in the inner core, most cells were electron dense (dark), showing frequent apoptotic and degenerative events; the outer epithelium-like sheet, was formed by low electron dense cells (light flat cells; LFCs) showing signs of intense metabolic activity, abundant cytoplasmic organelles, phagosomes, lysosome-like structures, apical microvilli, and filament bundles of cytoskeleton elements, indicating that LFCs play a role in extracellular exchanges. Apical-basal polarization of LFCs evidenced by frequent intercellular contacts, like adherens junctions and cytoplasmic interdigitations, was lost in some cells whose contacts with neighboring cells were loose intedigitations and expanded cytoplasmic processes. This might anticipate disengaging/aggregating of light protruding cells (LPCs) from/to the neurosphere, as consistently observed in cultures by inverted microscopy. Conclusions: Neurospheres spontaneously generated from ovarian cortical cells in culture, share most structural and ultrastructural characteristics of neurospheres derived from the CNS.

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Section: Discussionmentioning

confidence: 99%

Structure and ultrastructure of neurospheres spontaneously generated in culture from sheep ovarian cortical cells.

Salvador¹,

Maldonado²,

Galicia³

et al. 2019

Preprint

View full text Add to dashboard Cite

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“…The polarity of the endothelial cells plays a key role in maintaining the integrity of the BBB, being involved in counteracting the access of polar compounds, pathogens and immune cells to brain tissue [30]. The figure 3 shows localization of the luminal and abluminal sides of brain endothelial cells.…”

Section: The Polarisation Processmentioning

confidence: 99%

“…The brain endothelium polarity is also crucial for the preservation of the BBB integrity; in fact, it controls the expression and function of the intercellular junction proteins [30]. In turn, endothelial junctions play a fundamental role for the preservation of polarity [39], thus demonstrating that both factors cooperate to ensure the optimal functionality of the BBB: the intercellular junctions provide connection sites for the components underlying the cell polarity and, vice versa, the polarity process controls the expression and function of the intercellular junction proteins [30].…”

Section: The Polarisation Processmentioning

confidence: 99%

The “Frail” Brain Blood Barrier in Neurodegenerative Diseases: Role of Early Disruption of Endothelial Cell to Cell Connections

Maiuolo

Gliozzi

Musolino

et al. 2018

Preprint

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The main neurovascular unit of the Blood Brain Barrier (BBB) consists of a cellular component, which includes endothelial cells, astrocytes, pericytes, microglia, neurons and oligodendrocytes, as well as a non-cellular component resulting from the extracellular matrix. The endothelial cells are the major vital component of the BBB able to preserve the brain homeostasis; these cells are situated along the demarcation line between the bloodstream and the brain. Therefore, an alteration or the progressive disruption of the endothelial layer may clearly impair the brain homeostasis. The proper functioning of the brain endothelial cells is generally ensured by two elements: 1) the presence of junction proteins; 2) the preservation of a specific polarity involving an apical-luminal and a basolateral-abluminal membrane. In view of the above, this review intends to identify the molecular mechanisms underlying BBB function and their changes occurring in early stages of neurodegenerative processes in order to develop novel therapeutic strategies aimed to counteract neurodegenerative disorders.Preprints (www.preprints.org) | NOT PEER-REVIEWED | Posted:Here, we will review physiological mechanisms underlying endothelial cell tight connection and functioning in BBB and their impairment in the development of BBB "frailty" and neurodegenerative diseases. Junction Proteins of the Endothelial CellsJunction proteins involve "Tight Junctions (TJ)", "Adherens Junctions (AJ)" and "gap junctions."Gap junctions are responsible for intercellular communication and can even be lacking, while TJ and AJ proteins control the permeability of the endothelium [7]. Figure 1 summarizes the localization of endothelial junction proteins and their potential role under physiological conditions. Tight junctions complexThe TJ complex is composed of three types of integral membrane proteins: a) claudins, b) occludins and c) junctional adhesion molecules (JAMs), to which some auxiliary cytoplasmic proteins, such as ZO-1, ZO-2, ZO-3 and cingulins, are added. The TJ complex is located in the apical region of the endothelial cells and its proteins act as an inter-endothelial demarcation between the apical and the basolateral side of the cell, thus showing an asymmetric distribution of the membrane components [8].The junctional proteins are located at the lateral membrane of the adjacent endothelial cells and, on the basis of their reciprocal interaction, are able to seal the intercellular gaps, while the auxiliary cytoplasmic proteins establish a connection between the junction proteins and the intracellular cytoskeletal proteins. This is the pre-requisite to ensure the functional and structural integrity of the endothelium, thereby maintaining BBB selective permeability and counteracting an excessive infiltration of immunocompetent cells in the brain tissue [8]. ClaudinsThe family of claudins is composed of 26 isoforms, although the most common ones are claudin 1, claudin 3, claudin 5 and claudin 12 [9]. The proteins belonging to this large family have a m...

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“…The tightness of TJ in BBB ECs is regulated by interactions with astrocytes, pericytes and the extracellular matrix (ECM) (see section 5). Like epithelial cells, BBB ECs display a polarized distribution of receptors and transporters between the luminal and abluminal side that use energy to transport a net amount of fluid into the brain interstitium (Abbott 2004; Mokgokong et al 2014; Zhao et al 2015; Worzfeld and Schwaninger 2016); the mechanisms that control EC polarization remain largely unknown.…”

Section: Variations In the Organization Of Organ-blood Barriersmentioning

confidence: 99%

Directional Fluid Transport across Organ–Blood Barriers: Physiology and Cell Biology

Caceres

Benedicto

Lehmann

et al. 2016

Cold Spring Harb Perspect Biol

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Directional fluid flow is an essential process for embryo development as well as for organ and organism homeostasis. Here, we review the diverse structure of various organ-blood barriers, the driving forces, transporters and polarity mechanisms that regulate fluid transport across them, focusing on kidney-, eye- and brain-blood barriers. We end by discussing how cross-talk between barrier epithelial and endothelial cells, perivascular cells and basement membrane signaling contribute to generate and maintain organ-blood barriers.

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Apicobasal polarity of brain endothelial cells

Cited by 74 publications

References 208 publications

Structure and ultrastructure of neurospheres spontaneously generated in culture from sheep ovarian cortical cells.

Structure and ultrastructure of neurospheres spontaneously generated in culture from sheep ovarian cortical cells.

The “Frail” Brain Blood Barrier in Neurodegenerative Diseases: Role of Early Disruption of Endothelial Cell to Cell Connections

Directional Fluid Transport across Organ–Blood Barriers: Physiology and Cell Biology

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Apicobasal polarity of brain endothelial cells

Cited by 74 publications

References 208 publications

Structure and ultrastructure of neurospheres spontaneously generated in culture from sheep ovarian cortical cells.

Structure and ultrastructure of neurospheres spontaneously generated in culture from sheep ovarian cortical cells.

The &ldquo;Frail&rdquo; Brain Blood Barrier in Neurodegenerative Diseases: Role of Early Disruption of Endothelial Cell to Cell Connections

Directional Fluid Transport across Organ–Blood Barriers: Physiology and Cell Biology

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The “Frail” Brain Blood Barrier in Neurodegenerative Diseases: Role of Early Disruption of Endothelial Cell to Cell Connections