The dendritic tree, a highly branched structure of neurons, plays an important role in these brain functions. The dendrites act like antennae to receive signals from other cells and send them on to the nerve cell body. Congenital neurological conditions, like mental retardation, are often associated with errors in dendritic tree development.
Marta Rosário’s research team, in cooperation with Victor Tarabykin from Charité and Walter Birchmeier from MDC, has now discovered how this branching process is controlled during development. In living mice, it could be shown that the NOMA-GAP protein serves as a switch in this process. Maturing neurons produce this switch protein, which then starts a chain of signals in cells that leads to dendritic branching. A central element of this signal chain is a protein, called Cdc42. It plays an important role in the first developmental stages of neurons, but inhibits the branching of the dendritic tree in later developmental stages. When NOMA-GAP becomes active, it turns off Cdc42 allowing maturing neurons to form complex dendritic trees. The correct deployment of the switch protein and control of the signal chain regulated by Cdc42 are thus essential for the proper dendritic branching of neurons and thus for the development of the neocortex (the cerebral cortex) that steers sensory perception, memory, speech and movement, among other functions.
“Errors in this signal cascade lead to an incompletely developed dendritic tree. The result is a risk of mental limitations as signals in the brain cannot be adequately processed,” explains Marta Rosário. “For us the study forms an important foundation for researching various conditions, like mental retardation, schizophrenia or depression, that will hopefully point out new therapeutic avenues.”
NeuroCure is a Cluster of Excellence at Charité – Universitätsmedizin Berlin funded by the federal and state government within the framework of the Excellence Initiative. The focus of the interdisciplinary research network is to translate basic neuroscientific research findings into clinical application. Understanding the mechanisms of disease contributes to developing effective therapies for neurological illnesses like stroke, multiple sclerosis and epilepsy but also for psychiatric disorders such as Alzheimer´s and autism. In addition to Charité, the Humboldt-Universität zu Berlin, Freie Universität Berlin, Max Delbrück Center for Molecular Medicine (MDC), Leibniz Institute for Molecular Pharmacology (FMP), and Deutsche Rheuma-Forschungszentrum Berlin (DRFZ) are all NeuroCure partners.
Neocortical dendritic complexity is controlled during development by NOMA-GAP-dependent inhibition of Cdc42 and activation of cofilin
Marta Rosário,1,2,5 Steffen Schuster,1 René Jüttner,3 Srinivas Parthasarathy,1 Victor Tarabykin,1,4 and Walter Birchmeier2,4
1Neurocure Excellence Cluster, Institute of Cell and Neurobiology, Charité Universitätsmedizin Berlin, 10115 Berlin, Germany; 2Department of Signal Transduction, Invasion, and Metastasis of Epithelial Cells, 3Department of Developmental Neurobiology, Max Delbrück Center for Molecular Medicine, 13092 Berlin, Germany
4These authors contributed equally to this work.