The focus of this thesis has been the study of the cellular mechanisms regulating the neuromuscular junction organization in development, mature and disease state. As communication bridges between nervous cells, synapses are a key component of the nervous system, and thought to mediate important aspects of its function. The neuromuscular junction (NMJ) is an attractive synapse model, because of its ease of access for experimental purposes. The work described in this thesis yielded three major insights: 1 - In development, we have shown that synaptogenesis follows two different pathways in two newly identified muscle types. In FaSyn muscels synaptogenesis is rapid, whereas in DeSyn muscles formation of mature looking NMJs is delayed until birth. These two pathways of synapse maturation are regulated by muscle type and independent of nerve (chapter 10). 2 - In mature NMJs, we have shown taht local axon growth is tightly regulated by its postsynaptic partner in a process coupled to the state of postsynaptic receptor complex assembly (chapter 11). 3 - In a mouse model of Amyotrophic Lateral Sclerosis, we have shown that the disease process affects the motoneuron axon in a stereotyped manner, and that different types of motoneurons show selective vulnerability to the pathogenesis process (chapter 12).