As differential gene expression governs the progression of development into senescence, we attempted to define the genes that are selectively expressed during postnatal brain development. A cDNA fragment selectively expressed in neonatal rat brain was identified by differential display and used to screen a cDNA library prepared from the same mRNA sample. The full length cDNA, neuronatin, was 1195bp long and coded for a novel protein of 81 amino acids. The cDNA detected an mRNA species of similar size that was highly expressed in rat neonatal and human fetal brain. The deduced protein exhibited a hydrophobic N-terminal and hydrophilic C-terminal, suggesting that it is membrane bound and might function in signal transduction. The selective expression of this novel mRNA in late fetal and early postnatal brain development, and loss of expression in adulthood and senescence, suggests that downregulation of neuronatin may be involved in terminal brain differentiation.