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Wiring the extraocular muscles: mechanisms underlying normal innervation and abnormal innervation with reference to human Duane's syndrome

Funder: Wellcome TrustProject code: 076708
Funded under: Neuroscience and Mental Health Funder Contribution: 204,395 GBP

Wiring the extraocular muscles: mechanisms underlying normal innervation and abnormal innervation with reference to human Duane's syndrome

Description

A critical unsolved scientific question is how the nervous system gets wired up. Clues lie in embryonic development, when nerve cells (neurons) send out long thread-like structures called axons. Such challenging journeys are undertaken the axons of motor neurons, which lie inside the brain and spinal cord, but send their axons to connect with muscles in distant places such as limbs. Our research will concentrate on the connections of motor nerves which control eye muscles. During normal development each nerve reaches its correct muscle(s) and avoids incorrect ones, while in a human condition called Duane's syndrome, this process goes wrong and the nerves become miswired, leading to squint. We will discover the molecular "code" that guides axons to the correct muscle, identify molecules responsible for Duane's syndrome, and discover whether they affect predominantly nerve or muscle development. Gene screening techniques will be used to identify molecules which distinguish the different eye muscles. We will either reduce or increase the levels of these molecules, in order to see the effects on nerve growth and the formation of connections. In this way the molecular events which lead to a correct wiring pattern, and those which are disrupted in some human patients, will be unravelled

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