Scientists from Imperial College London and King’s College London have identified a molecule that helps to wire up the neural circuitry responsible for controlling the movement of muscle.
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.
1. Title: WNT-3 Expressed by Motorneurons, Regulates Terminal Arborization of Neutrophin-3-responsive Spinal Sensory Neurons.
Authors: Olga Krylova, Judit Herreros, Karen E Cleverley, Elisabeth Ehler , Juan Pablo Henriquez, Simon M Hughes and Patricia C. Salinas.
MRC Centre for Developmental Neurobiology, 4th floor New Hunt’s House, Guys Campus, King’s College London, SE7 1UL, UK.
Department of Biological Sciences, Faculty of Life Sciences, Imperial College London, SW7 2AZ.
2. King’s College London is one of the oldest and largest colleges of the University of London with some 12,400 undergraduate students and over 4,700 postgraduates in ten schools of study. The College had 24 of its subject-areas awarded the highest rating of 5* and 5 for research quality, demonstrating excellence at an international level. It is in the top group of five universities for research earnings and has an annual turnover of over £300 million and research income from grants and contracts in excess of £87 million (2000-2001).
3. Consistently rated in the top three UK university institutions, Imperial College London is a world leading science-based university whose reputation for excellence in teaching and research attracts students (10,000) and staff (5,000) of the highest international quality. Innovative research at the College explores the interface between science, medicine, engineering and management and delivers practical solutions, which enhance the quality of life and the environment – underpinned by a dynamic enterprise culture. Website: www.imperial.ac.uk