| During embryonic development, motor neurons, whose cell bodies are contained within the spinal cord, extend axons that contact only one of over more than fifty muscles present in the limb. In Chapter One, I discuss the cellular strategies utilized by motor axons to reach their targets and the molecular programs that control axon guidance choice. I also describe how these molecular programs may regulate muscle target selectivity.; The subset of motor neurons that project to a single muscle target constitutes a motor neuron pool in the spinal cord. This motor pool identity determines the pattern of muscle innervation. In Chapter Two, I demonstrate that the ETS family of transcription factors appears not to be involved in the decisions required to project to specific muscles. In contrast, I found that Nkx6.1, a member of the Nkx6 family of transcription factors, defines motor neuron pools and regulates the selectivity of muscle nerve projections. In Chapter Three, I show that loss of Nkx6.1 function causes motor axons to project to muscles targets normally reserved for motor pools that lack Nkx6.1 expression. Conversely, ectopic expression of Nkx6.1 in motor neurons that normally lack Nkx6.1 expression causes motor axons to project to targets normally reserved for motor pools that express Nkx6.1. These findings provide genetic evidence that Nkx6 genes ensure the fidelity of motor axon trajectories in the developing limb.; A remarkable feature of motor neurons within a given motor neuron pool is their ability to cluster into discrete groups within the spinal cord. In Chapter Four, I discuss the experimental evidence that has implicated the ETS genes and their downstream targets, the Type II cadherins, in the motor neuron pool sorting and clustering.; Transcription factors may exert their influence on axon guidance trajectories by regulating the expression of axon guidance receptors. In Chapter Five, I provide evidence that Npn2, a member of the neuropilin family of semaphorin co-receptors, is expressed in ventrally projecting motor neurons and regulates their projection towards the ventral limb compartment. |
