HMG BOX-CONTAINING TRANSCRIPTION FACTORS IN LYMPHOCYTE DIFFERENTIATION

The identification of the mammalian sex-determining gene Sry has led t o the discovery of a large family of related ('HMG box') transcription factors that control developmental events in yeast, C. elegans, Droso phila and vertebrates. In lymphocyte differentiation, several HMG box proteins play a decisive role. Sox-4 is important for very early B-cel l differentiation while TCF-1/LEF-1 play a crucial role in early thymo cyte development. TCF/LEF proteins have recently been found to constit ute a downstream component of the Wingless/Wnt signal transduction pat hway. In flies, this pathway controls segment polarity; in Xenopus if controls the definition of the body axis. Deregulation of the pathway occurs in several human tumors. These insights in the molecular events that are involved in TCF/LEF function in these organisms may eventual ly lead to the understanding of the function of these HMG box proteins in lymphoid development.