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Salivary gland bioengineering requires understanding the interaction between salivary epithelium and surrounding tissues. An important component of salivary glands is the presence of neurons. No previous studies have investigated how neurons and salivary epithelial cells interact in an in vitro co-culture model. In this study, we describe the self-organization of neurons around salivary epithelial cells in co-culture, in a similar fashion to what occurs in native tissue. We cultured primary mouse cortical neurons (m-CN) with a salivary epithelial cell line (Par-C10) on growth factor-reduced Matrigel (GFR-MG) for 4 days. After this time, co-cultures were compared with native salivary glands using confocal microscopy. Our findings indicate that m-CN were able to self-organize basolaterally to salivary epithelial cell clusters in a similar manner to what occurs in native tissue. These results indicate that this model can be developed as a potential platform for studying neuron-salivary epithelial cell interactions for bioengineering purposes.