Final Report Summary - MU TUNING (Fine Tuning the Final Common Pathway: Molecular Determinants of Motor Unit Development and Plasticity)
Our ability to control limbs and body, be it when walking or dancing, operating a sledge hammer or playing the piano, relies on specialized nerve cells, called motor neurons that directly link nervous system and skeletal muscle. It has been known since over 70 years that the accurate translation of electrical impulses from the brain into smooth movements involves “teamwork” between a range of different motor neuron types. Despite their importance for movement control, the mechanisms underlying the diversification of the motor neuron types remained unknown. The project systematically analyzed the activity of thousands of genes in the different motor neuron types. We
thereby identified three genes as the first known determinants of motor neuron functional diversification. A gene called Dlk1, for instance, tuned the electrical of motor neurons to generate brief bursts of high muscle force, such as during jumping or weight-lifting. Another pair of genes we identified, in contrast, tuned motor neuron function to enable skilled movements, such as balancing on a beam. The project further resolved mechanisms through which genes such as these influence neuronal properties and thereby offers a potential means to alter their vulnerability in fatal disease affecting motor neurons, such as ALS. The project thus provided first insights into the mechanisms that allow motor neurons acquire different functions for granting our brain accurate control over the movement apparatus, which we hope will also inspire novel strategies for treating diseases of the nervous system.
thereby identified three genes as the first known determinants of motor neuron functional diversification. A gene called Dlk1, for instance, tuned the electrical of motor neurons to generate brief bursts of high muscle force, such as during jumping or weight-lifting. Another pair of genes we identified, in contrast, tuned motor neuron function to enable skilled movements, such as balancing on a beam. The project further resolved mechanisms through which genes such as these influence neuronal properties and thereby offers a potential means to alter their vulnerability in fatal disease affecting motor neurons, such as ALS. The project thus provided first insights into the mechanisms that allow motor neurons acquire different functions for granting our brain accurate control over the movement apparatus, which we hope will also inspire novel strategies for treating diseases of the nervous system.