Defective intercellular connections cause hydrocephalus
A defective gene leads to changes in the cellular layer between cerebrospinal fluid and brain nervous tissue, thus causing a buildup of fluid in the brain. This link, which scientists from the German Cancer Research Center in Heidelberg have now discovered, is the first known mechanism underlying genetic hydrocephalus.
Scanning electron microscopy image of impaired ependymal cell layer within a brain ventricle following loss of Mpdz gene
© Anja Feldner, Manfred Ruppel, DKFZ
About one in 2,000 babies are born with hydrocephalus, a condition in which cerebrospinal fluid (CSF) cannot flow towards the spinal column and builds up instead in the cavities (ventricles) of the brain. This causes the head to swell like a balloon and puts pressure on the brain. Various neurological symptoms can occur as a result including headache, vomiting, impaired vision, loss of coordination, seizures and cognitive difficulties. There are various causes of hydrocephalus. In some cases the condition is caused by a genetic abnormality.
The research team led by Andreas Fischer from the German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ) in Heidelberg already discovered in 2013 that a defect in a gene called Mpdz causes hydrocephalus in mice. In the same year, scientists from Saudi Arabia identified its human counterpart as a genetic cause of hydrocephalus in humans.
Now Fischer and his team have been able to uncover the mechanism underlying this genetic defect. The scientists observed in newborn mice with defective Mpdz that the ependyma, a cellular layer separating the brain nervous tissue from the CSF, is severely damaged. In order to maintain this vital dividing line, cells of a different type, called astroglia, fill in and ensure that the dividing tissue layer remains stable. However, this has a high price: Scar tissue develops in the ependyma leading to blockage of the so-called aqueduct, a channel connecting two ventricles of the brain, thus blocking the flow of cerebrospinal fluid.
"Evidence suggests that loss of the Mpdz gene reduces the stability of so-called tight junctions between adjacent ependymal cells, explains Anja Feldner, who is the first author of the study. The gene product of Mpdz controls molecules that play a crucial role for the stability of tight junctions. In fact, experiments in the Petri dish have shown that these junctions are impaired between ependymal cells with defective Mpdz. "This means we have uncovered a crucial mechanism that underlies the onset of genetic hydrocephalus," Fischer commented.
Anja Feldner, M. Gordian Adam, Fabian Tetzlaff, Iris Moll, Dorde Komljenovic, Felix Sahm, Tobias Bäuerle, Hiroshi Ishikawa, Horst Schroten, Thomas Korff, Ilse Hofmann, Hartwig Wolburg, Andreas von Deimling and Andreas Fischer: Loss of Mpdz impairs ependymal cell integrity leading to perinatal-onset hydrocephalus in mice. EMBO Molecular Medicine, 2017, DOI: 10.15252/emmm.201606430
An image for this press release is available at:
http://www.dkfz.de/de/presse/pressemitteilungen/2017/bilder/Feldner-Mpdz.jpg
Caption: Scanning electron microscopy image of impaired ependymal cell layer within a brain ventricle following loss of Mpdz gene.
Note on use of images related to press releases
Use is free of charge. The German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ) permits one-time use in the context of reporting about the topic covered in the press release. Images have to be cited as follows: "Source: Anja Feldner, Manfred Ruppel, DKFZ".
Distribution of images to third parties is not permitted unless prior consent has been obtained from DKFZ's Press Office (phone: ++49-(0)6221 42 2854, E-mail: presse@dkfz.de). Any commercial use is prohibited.
With more than 3,000 employees, the German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ) is Germany’s largest biomedical research institute. DKFZ scientists identify cancer risk factors, investigate how cancer progresses and develop new cancer prevention strategies. They are also developing new methods to diagnose tumors more precisely and treat cancer patients more successfully. The DKFZ's Cancer Information Service (KID) provides patients, interested citizens and experts with individual answers to questions relating to cancer.
To transfer promising approaches from cancer research to the clinic and thus improve the prognosis of cancer patients, the DKFZ cooperates with excellent research institutions and university hospitals throughout Germany:
The DKFZ is 90 percent financed by the Federal Ministry of Education and Research and 10 percent by the state of Baden-Württemberg. The DKFZ is a member of the Helmholtz Association of German Research Centers.
