Although transcriptional factors are known to play important roles in synaptic plasticity, their role in olfactory adaptation has not been studied well. Here we report that Ce-TBX-2, the TBX2/TBX3 transcriptional factor homologue of the nematode Caenorhabditis elegans, is involved in olfactory adaptation. Two missense hypomorphic mutations in this gene confer abnormality in adaptation, but not chemotaxis, to all the odorants sensed by AWC olfactory neurons. The Ce-tbx-2 gene is expressed in AWB, AWC, ASJ, and many pharyngeal neurons, but expression in AWC neurons is sufficient for normal adaptation. Unexpectedly, the protein product is localized mostly in cytoplasm. The AWC neurons in the mutants retain their characteristic morphology and many marker gene expressions, suggesting that the mutants are abnormal in neural functions rather than neuronal differentiation. The results of this study imply that some of the mammalian T-box family proteins, which play central roles in embryonic development, may also control functions like neural plasticity in differentiated neurons. (C) 2003 Wiley Periodicals, Inc. J Neurobiol 58: 392-402, 2004.