Our daily life is filled with locomotion and emotion, two processes controlled by our sophisticated and delicate nervous system. During development, billions of neurons make connections with specific synaptic partners in both central and peripheral nervous systems. How such specificity is achieved and maintained is a long-standing question in neurobiology. A prevailing hypothesis is that cell surface proteins function as a “lock-and-key” to guide the recognition between pre- and postsynaptic neurons. We focus on two Drosophila immunoglobin subfamilies, the Dprs (defective proboscis extension response, 21 members) and DIPs (Dpr-interacting proteins, 11 members). Dprs and DIPs can form homophilic or heterophilic interactions, and these interactions are proposed to guide synaptic recognition. A small subset of Dprs and DIPs have been examined in larvae and adults, but most Dpr-DIP pairs have not been studied, in part, due to the likely redundancy and their unknown expression patterns. To gain a deeper understanding of Dprs and DIPs, I conducted an expression profiling. We generated a Dpr/DIP GAL4 collection and examined their expression in larval sensory neurons and the neuromuscular system. I described detailed expression maps of each dpr and DIP in all larval sensory neurons, motor neurons, glial cells, and muscles. I found that similar neurons express similar dprs and DIPs. In addition, I uncovered previously unidentified motor neurons using these GAL4 lines and found specific dprs and DIPs that are required for synaptic recognition. In summary, the expression map and the GAL4 lines will provide the field an entry point and a genetic toolbox to explore the functions of Dprs and DIPs. Dpr-DIP interactions were implicated in synaptic connectivity, and we wondered whether neuromuscular function was also affected when perturbing connectivity. In the Drosophila larval neuromuscular system, each muscle normally receives two glutamatergic motor neuron inputs. We asked whether loss of one input will perturb synaptic function or instead, will induce morphological and/or functional compensatory changes from the nearby motor neuron input. Interestingly, we found that ablation of one neuron significantly induced morphological and functional compensation from adjacent healthy neurons – a process we termed “cross-neuron plasticity”. We examined multiple motor neuron-muscle pairs and found different motor neurons have different compensability. Next, we investigated the mechanism underlying cross-neuron plasticity and found that an engulfment receptor, Draper, is required. In draper mutants, significant debris from degenerating neurons accumulated in glial cells and healthy neurons lose both morphological and functional plasticity, suggesting that Draper is required to transmit a signal to nearby healthy neurons. This study has implications for neurodegenerative diseases marked by synaptic dysfunction and eventual neuron death as cross-neuron plasticity could provide compensatory functional changes from the remaining neurons. Taken together, my Ph.D. work focused on Dpr-DIP mediated synaptic recognition and cross-neuron plasticity. I described the expression of dprs and DIPs in the Drosophila larval nervous system and identified a new type of synaptic plasticity which empowers healthy neurons to respond to nearby neuronal cell death. These studies have expanded our understanding of synaptic connectivity and plasticity and have generated many exciting, testable hypotheses.