To establish a better understanding of the neonatal mammalian digit tip regeneration response, a custom cDNA microarray consisting of regeneration specific genes was created. Combinations of several normalizations were used to account for biases inherent in the array. From this subset of clones, one gene found to be differentially expressed in non-regenerating digits was Keratin 6b. Keratin 6b mRNA was seen in the entire wound edge of non-regenerating digits but only on the ventral side of the regenerating digit. Further analysis found that Keratin 6b is expressed in a symmetrical pattern in embryonic regenerating digits, suggesting that wound healing is different between the neonate and embryonic regeneration responses. During the embryonic analysis it was also shown that Keratin 6b is present in the digit pulp of developing and mature digits Analysis of the genes up regulated in regenerating digits as opposed to non-regenerating digits also identified several genes, two of which were Keratin 1--4 and Keratin Associated Protein 6.1, as differentially expressed. Further analysis of the embryonic expression pattern of these genes showed that they are early markers for dorsal nail bed and nail plate Since Msx genes play a critical role in the digit regeneration response, the 3 keratins found in the microarray analysis were examined in the Msx-/- mutant mice. All gene expression remained unmodified, suggesting that none of these genes are downstream of the Msx genes This study demonstrated the validity of the custom cDNA microarray. There are 17 clones yet to be sequenced from the microarray analysis and could lead to critical genes in the regeneration process being found