Speech, sensory perception, thought formation, decision-making processes and movement are complex tasks that the brain only masters when individual nerve cells (neurons) are well connected. Berlin neuroscientists have now discovered a molecular switch that regulates this networking of nerve cells.
The scientists from Charité -- Universitätsmedizin Berlin, the NeuroCure Cluster of Excellence and the Max Delbrück Center for Molecular Medicine (MDC) have published their work in the journal Genes and Development.
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."
- M. Rosario, S. Schuster, R. Juttner, S. Parthasarathy, V. Tarabykin, W. Birchmeier. Neocortical dendritic complexity is controlled during development by NOMA-GAP-dependent inhibition of Cdc42 and activation of cofilin. Genes & Development, 2012; DOI: 10.1101/gad.191593.112
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