Retinoic Acid Induces Blood–Brain Barrier Development

Mizee, Mark R.; D, Wooldrik; Lakeman, Kim; Hof, Bert van het; Drexhage, Joost; Geerts, Dirk; Bugiani, Marianna; Aronica, Eleonora; Mebius, Reina E.; Prat, Alexandre; Vries, Helga E. de; Reijerkerk, Arie

doi:10.1523/jneurosci.1338-12.2013

Cited by 176 publications

(162 citation statements)

References 59 publications

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“…The Blood -Brain Barrier Cite this article as Cold Spring Harb Perspect Biol 2015;7:a020412 in a perturbed BBB (Mizee et al 2013). Interestingly, RA is known to regulate the Hh, Wnt, and FGF pathways (Halilagic et al 2007;Paschaki et al 2012), which implies that RA secretion by radial glial cells could be a master upstream regulator of BBB development.…”

Section: Regulation Of the Bbb By Astrocytesmentioning

confidence: 99%

The Blood–Brain Barrier

Daneman

Prat

2015

Cold Spring Harb Perspect Biol

2,533

1,829

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Blood vessels are critical to deliver oxygen and nutrients to all of the tissues and organs throughout the body. The blood vessels that vascularize the central nervous system (CNS) possess unique properties, termed the blood-brain barrier, which allow these vessels to tightly regulate the movement of ions, molecules, and cells between the blood and the brain. This precise control of CNS homeostasis allows for proper neuronal function and also protects the neural tissue from toxins and pathogens, and alterations of these barrier properties are an important component of pathology and progression of different neurological diseases. The physiological barrier is coordinated by a series of physical, transport, and metabolic properties possessed by the endothelial cells (ECs) that form the walls of the blood vessels, and these properties are regulated by interactions with different vascular, immune, and neural cells. Understanding how these different cell populations interact to regulate the barrier properties is essential for understanding how the brain functions during health and disease.

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Section: Regulation Of the Bbb By Astrocytesmentioning

confidence: 99%

The Blood–Brain Barrier

Daneman

Prat

2015

Cold Spring Harb Perspect Biol

2,533

1,829

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“…Although the differentiation efficiency was not affected by the addition of RA, total cell proliferation was increased, leading to a higher number of BMECs [43,55]. RA is secreted by radial glia during brain development and is crucial for the development of a tight BBB during mouse development as well as in BMEC lines [56]. Within cells, it is bound by retinol-binding protein that is expressed in BMECs in vivo and also binds to the nuclear receptor STRA6 [57].…”

Section: Psc Differentiation Into Nvu Cell Typesmentioning

confidence: 99%

Paving the Way Toward Complex Blood-Brain Barrier Models Using Pluripotent Stem Cells

Lauschke

Frederiksen

Hall

2017

Stem Cells and Development

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“…The embryos of BMS193-treated mice showed higher BBB permeability, decreased levels of RARb gene-expression, and decreased gene-expression of ZO-1 and VE-cadherin, while gene-expression of occludin and claudin-5 remained unaffected. 49 Similar effects were described using brain microvascular endothelial cells derived from human pluripotent stem cells (hPSCs), indicating that RA is a potent stimulator of BBB function. 50 Several studies have shown aberrant RA signaling in the brains of AD patients.…”

Section: Retinoic Acidmentioning

confidence: 66%

“…Treatment with RA increased the expression of TJ proteins and induced high transendothelial electrical resistance (TEER), while decreasing levels of the permeability-inducing factor VEGF-A (vascular endothelial growth factor A). 49 Effects were predominantly mediated by RARb, the most important receptor in CNS specific RA signaling. In addition to a role for RARb in barrier integrity, RARb also plays a role in the development of the BBB.…”

Section: Retinoic Acidmentioning

confidence: 99%