Sealed off

Researchers of the Max Delbrück Center (MDC) and the Leibniz Institute for Molecular Pharmacology (FMP) in Berlin-Buch, have now demonstrated how these brain ventricles develop prior to the establishment of the blood-brain barrier in zebrafish.

One specific protein (Claudin5a) is decisive for this development. It forms a barrier between the nervous tissue and the ventricles. If it is absent, the ventricles cannot expand and the brain morphogenesis of the animals is disrupted. These insights could be used to test the penetrability of drugs into the brain. (PNAS).

Like the blood-brain barrier, which prevents pathogens from penetrating into the brain via the blood, the brain ventricles are also isolated from their surroundings by a cerebral-ventricular barrier. Thus, the ventricles can fill with fluid, expand and in this way contribute to the stability of the brain. In contrast to the blood-brain barrier, the cerebral-ventricular barrier does not contain any blood vessels, but rather consists exclusively of neurons interwoven with each other via protein filaments. One component of these tightly woven filaments, the tight junctions, is the protein Claudin5a.

Jingjing Zhang of the research group of Dr. Salim Seyfried (MDC) and scientists belonging to the research group of Dr. Ingolf E. Blasig (FMP) have now for the first time identified the function of this protein during an early stage of zebrafish development. Their experiments revealed that the ventricles did not expand when Claudin5a was absent. The consequence – the brain morphology was altered. However, when the scientists re-established the function of Claudin5a by switching Claudin5a on in the entire embryo, the brain ventricles were able to expand again.

Dr. Seyfried is convinced that these findings on barrier tightness by Claudin5a could also be useful for pharmacological research. Drugs hardly ever penetrate the blood-brain barrier, which makes treatment of brain diseases difficult. “Further studies on zebrafish could help to identify substances that switch off the function of Claudin5a for a short time and thus contribute to the opening of brain barriers such as the blood-brain barrier. This could be significant for the development of drugs intended to unfold their effect in the brain.”

* Establishment of a neuroepithelial barrier by Claudin5a is essential for zebrafish brain ventricular lumen expansion
Jingjing Zhang1, Jörg Piontek2, Hartwig Wolburg3, Christian Piehl2, Martin Liss1,2, Cécile Otten1, Annabel Christ1, Thomas E. Willnow1, Ingolf E. Blasig2,# and Salim Abdelilah-Seyfried1,#
1Max Delbrück Center (MDC) for Molecular Medicine, Robert-Rössle Str. 10, D-13125 Berlin, Germany
2Leibniz Institute for Molecular Pharmacology, Robert-Rössle Str. 10, D-13125 Berlin, Germany
3Institute of Pathology, University of Tübingen, Liebermeisterstr. 8, D-72076 Tübingen, Germany

#Corresponding authors

Barbara Bachtler
Press and Public Affairs
Max Delbrück Center for Molecular Medicine (MDC) Berlin-Buch
Robert-Rössle-Straße 10; 13125 Berlin; Germany
Phone: +49 (0) 30 94 06 – 38 96
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e-mail: presse@mdc-berlin.de