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.

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.

The article, "Loss of Mpdz impairs ependymal cell integrity leading to perinatal–onset hydrocephalus in mice," was published in the journal EMBO Molecular Medicine.