We here study the expression patterns of the cell adhesion molecules nectin-1, nectin-3, N-cadherin, and neural cell adhesion molecule (NCAM) in motoneurons after sciatic nerve transection (SNT). Nectins are a newly discovered family of adhesion molecules that colocalize with N-cadherin in synapses and are expressed in axons during development. By in situ hybridization (ISH), we found nectin-3, N-cadherin, and NCAM mRNA in uninjured motoneurons. In uninjured animals, nectin-3 mRNA was present in a few vesicular acetylcholine transporter (VAChT)-positive cells of small motoneuron size in lamina IX of the spinal cord. SNT induced a significant increase of nectin-1, nectin-3, and NCAM mRNA, but the signal for N-cadherin mRNA was not affected. After SNT, signal for nectin-3 mRNA appeared over most motoneurons. We next investigated the presence of N-cadherin and nectin protein in synapses on spinal motoneurons by immunohistochemistry. Only N-cadherin immunoreactivity was seen in close relation to synaptophysin staining, while nectin-1 and nectin-3 immunoreactivity did not display such proximity. SNT resulted in decreased immunoreactivity for N-cadherin around the motoneuron soma, while nectin-1 and nectin-3 immunoreactivity remained unchanged. In the peripheral sciatic nerve, nectin-3 immunoreactivity was observed both in controls and following injury and nectin-3 colocalized with both neurofilament and the Schwann cell marker S100. In addition, an increased ISH signal for nectin-3 mRNA could be seen over the proximal stump of the sciatic nerve after SNT. We conclude that motoneuron injury induces complex changes in the spatiotemporal expression pattern of the investigated cell adhesion molecules.