Charité researchers identify molecules that can steer nerve fiber growth
How do nerve fibers know where to grow and with which of the approximately hundred billion nerve cells of the brain they need to form connections? Scientists at Charité – Universitätsmedizin Berlin have taken us a step further towards addressing this question by identifying two molecules that control nerve fiber navigation during development of the brain. The results of their study are published in the current issue of Nature Communications*.
The brain is responsible for executing extremely complex tasks like processing sensory information, decision-making and generating speech and language. The neocortex, which forms the outermost part of the brain, is primarily involved in carrying out these higher brain functions. Nerve fibers form connections between the nerve cells (neurons) of the cerebral cortex and serve to link various regions of the nervous system with each other allowing for the exchange of neural information. Neurons of the neocortex, mainly, form two different types of connections; inter-hemispheric tracts like the corpus callosum, which connects the right hemisphere with the left hemisphere and sub-cortical tracts, which connects the neocortex to underlying structures such as the spinal cord.
Scientists working together with Prof. Dr. Victor Tarabykin, Acting Director of the Institute of Cell Biology and Neurobiology at the Campus Charité Mitte and Principal Investigator for the "Cluster of Excellence - Neurocure" at the Charité, have succeeded in decoding a molecular program, which controls how such connections are made. The team of scientists has established that, two proteins Satb2 and Ctip2 are capable of regulating the choice of a neocortical neuron to either connect through the corpus callosum or to connect to sub-cortical structures such as the spinal cord. They do so by regulating the levels of two other proteins called Unc5C and DCC. Unc5C and DCC in turn make the growing nerve fiber respond differently to the levels of another protein called Netrin1 present in the environment just below the neocortex.
"During the development phase, nascent axons respond to chemical signals, referred to as guidance cues, located in their immediate environment. These guidance cues can either exert a force of attraction that prompts the axons to grow towards the source, or they can have a repulsive effect and prevent axons from entering the area", explain Swathi Srivatsa and Srinivas Parthasarathy, the two lead authors in the study. "We have demonstrated that Satb2 and Ctip2 proteins function as molecular switches, which can help to steer the nerve fibers in a specific direction. The nerve fibers of Satb2 producing neurons also produce Unc5C, which is repelled by netrin1. These axons hence move away from the netrin1 source and in doing so form the corpus callosum. On the other hand the neurons producing Ctip2 also produce DCC, which is attracted to the netrin1 source. These nerve fibers hence move towards the region below the neocortex forming sub-cortical tracts."
Srivatsa S, Parthasarathy S, Britanova O, Bormuth I, Donahoo AL, Ackerman SL, Richards LJ, Tarabykin V. Unc5C and DCC act downstream of Ctip2 and Satb2 and contribute to corpus callosum formation. Nat Commun. 2014 Apr 17;5:3708. doi:10.1038/ncomms4708.
Prof. Dr. Victor Tarabykin
Kommissarischer Direktor Institut für Zell- und Neurobiologie
Campus Charité Mitte
t: +49 30 450 528 418
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