Transcription factors in mouse fetal thymus development

Abstract

T cell precursors from murine fetal liver enter the fetal thymus where they proliferate, differentiate, and mature. These processes are accompanied by changes in the pattern of transcription factors known to control the expression of specific genes. We have monitored the expression of five different transcription factors during mouse fetal thymus ontogeny: nuclear factor (NF)-kappa B, cAMP-response-element binding protein (CREB), NF-IL-2A, msNF-AT1, and hNF-AT1. NF-kappa B binding activity was not detected in extracts from fetal liver but was present in the thymus at day 14 of embryogenesis. Thereafter, NF-kappa B expression was biphasic, being maximal at 14-16 days gestation and in newborn mice, and decreased during the intermediate gestational stages and in the adult. An inverse correlation was observed between NF-kappa B binding activity in the nuclei and levels of its inactive precursor in the cytoplasm of all samples analyzed. In contrast, CREB activity was uniform throughout thymus development. Similarly, NF-IL-2A activity was detected in fetal liver and thymic extracts from different gestational stages, in approximately equivalent amounts. However, band shift experiments revealed three distinct NF-IL-2A-DNA complexes, whose relative abundance is altered during thymic ontogeny. Likewise, NF-AT1 transcription factor appears to be heterogeneous and includes representatives which are differentially (msNF-AT1) or stably (hNF-AT1) expressed during thymic development. These results are discussed in the context of present knowledge about T cell development within the thymus.