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New findings on inter-cellular communication

August 23rd 2018

By studying the development of the blood vessels of the brain, researchers from the Biopark have solved an important enigma in the field of cell signaling.

This is a nice example of a rather unexpected discovery: by studying the development of the blood vessels of the brain, researchers from the Biopark have solved an important enigma in the field of cell signaling.

Led by Benoit Vanhollebeke, the Laboratory of Neurovascular Signaling (Molecular Biology Department, IBMM) has found the molecular mechanism conferring ligand specificity to Wnt signaling, an ancestral communication pathway whose evolutionary appearance dates back to the emergence of multicellular animals. When dysfunctional, Wnt signaling can be at the origin of many diseases, in particular several cancers.

A lot of combinations

With 10 receptors and 19 ligands, recognizing each other, the complexity of the pathway seemed dizzying: how do vertebrate cells manage to interpret the many Wnt signals they encounter and trigger an adequate response? It is such an interpretation mechanism that ULB researchers have discovered and detailed in Science in late July.

Researchers were focused on Gpr124 and Reck, two proteins required for cerebrovascular development in response Wnt7 ligands. They conducted genetic, biophysical and zebrafish experiments, in collaboration with Abel Garcia-Pino’s team (cellular and molecular microbiology laboratory, Molecular Biology Department, IBMM), a team from Université catholique de Louvain and another from the Max Planck Institute for Heart and Lung Research (Germany). They have discovered that the complex Gpr12 /Reck acts as a decoding module: Reck recognizes the Wnt7 ligand, but the presence of Gpr124 is necessary to trigger Wnt7 signaling via Frizzled receptors.

Decoding modules

The specificity of Wnt signaling seems to hold within this multi-proteins « decoding modules », that interpret the many signals and trigger an adequate response. These discoveries will enable researchers to refine their understanding of Wnt signaling and its multiple regulations. This would also make it possible to consider new treatments for diseases, such as cancers or neurovascular diseases.