Neural Signal That Helps Wire Up Brain’s Movement Circuit Identified

Writing today in the journal Neuron, the researchers describe how the signalling protein named WNT-3 directs specific neurons during embryonic development to make the correct connections in the spine to form a neural pathway that controls muscle.

Using mice, which offer the closest model to human neurobiology, the scientists found that WNT-3 is only produced by motor neurons in the spinal cord at a crucial stage when sensory neurons come close to them.

"Assembling the components to connect any neural circuit is a complex process. During development of the brain and spinal cord a hundred million neurons are looking for their neural partners to make connections with," said Dr Patricia Salinas of Imperial's Department of Biological Sciences who led the study. "We found that motor neurons release the WNT-3 protein to guide sensory neurons to make connections with them."

The ability to collect and transmit information to the brain from the internal and external environment is dependent on the sensory system. Sensory neurons carry information about muscle tension and body position to motor neurons in the spinal cord to control muscle contraction.

The researchers took pieces of spinal tissue from embryonic mice and found that sensory neurons stop growing and begin to branch ready to form a functional connection or synapse when the WNT-3 signal is sent out.

Tissue culture studies confirmed that the presence of WNT-3 causes sensory neurons to remodel themselves in readiness for neurotransmission.

"The molecular identities of signals that regulate formation of specific connections between sensory and motor neurons were previously unknown. Understanding the complex web of instructions that direct this intricate process may have important implications for neural regeneration following spinal injury," said Dr Salinas.