Cytoplasmic distribution of T-box transcription factor Tbr-1 in adult rodent brain

Abstract

T-brain-1 (Tbr-1), a brain-specific T-box transcription factor, plays a critical role in cerebral cortex and olfactory bulb development. The expression levels of Tbr-1 are highest at the embryonic stage and are gradually reduced during the developmental process. In adult brain, Tbr-1 is expressed at a lower, but still significant level. Tbr-1 transcriptional activity is enhanced via interaction with CASK, a membrane-associated guanylate kinase, but it is not clear whether any other mechanism regulates Tbr-1 activity. We examined the subcellular distribution of Tbr-1 in adult and postnatal rat brains using DAB stain and confocal imaging analysis. In contrast to the embryonic stage, Tbr-1 was distributed in P3 and adult rat brain in the nucleus as well as the cytoplasm of neurons in the cerebral cortex and hippocampus. Confocal analysis clearly showed dendritic distribution of Tbr-1 in pyramidal neurons. In the cerebellum of P15, P22, and adult rats, Tbr-1 was specifically expressed in Purkinje cells, where Tbr-1 was localised in the cytoplasm, including the dendritic tree. In addition, biochemical fractionation of adult cerebral cortex and hippocampus showed that cytoplasmic Tbr-1 is highly enriched in the lysed synaptosomal fraction, further indicating a synaptic distribution of cytoplasmic Tbr-1 in adult brain. Our study suggests that translocation from synapse to the nucleus is involved in regulation of Tbr-1 function in postnatal and adult brains.