Segmental and developmental regulation of a presumptive T-cell oncogene in the central nervous system

Abstract

Although most proto-oncogenes such as c-myc are involved in cell proliferation, being expressed in a wide range of tissues as well as in progenitors of transformed cells, others may normally function in cellular differentiation. We now report on a gene on human chromosome 11, at the junction of the T-cell tumour-associated chromosomal translocation t(11; 14) (p15; q11) and known as the 11p15 gene or Ttg, which is believed to be involved in the pathogenesis of the tumour. It has two transcriptional promoters (both retained by the translocated allele) and is expressed in tumour cells with neuro-endocrine properties, suggesting that normal expression may occur in nerve cells. Using fusion constructs of one 11p15 promoter and lacZ in transgenic mice, we found that the gene is expressed in a segment-specific manner in rhombomeres of the developing mouse hind-brain. During subsequent development, the gene is more widely expressed, again in precisely defined regional patterns, but in post-mitotic neurons confined to the central nervous system. Thus, this presumptive T-cell oncogene is both developmentally regulated and segmentally restricted in a tissue different from that in which the original tumour arose.