Role of the Brachyury T gene in P19 embryonal carcinoma cell differentiation.

Abstract

Brachyury T is a gene required for mesoderm formation and is expressed early during gastrulation in presumptive mesoderm. We found that this gene is expressed transiently in P19 cells destined to differentiate into cells of the mesodermal lineages. The expression of Brachyury in P19 cells peaks two days after initiation of differentiation and is induced by cell aggregation. The formation of compact cell aggregates and the expression of Brachyury are both dependent on extracellular calcium. Activin A, bone morphogenetic proteins and cAMP all induced Brachyury expression. By contrast, leukaemia inhibitory factor significantly reduced Brachyury expression in aggregated P19 cells and inhibited differentiation. Overexpression of Brachyury in P19 cells leads to their spontaneous differentiation with low levels of Brachyury resulting in the development of skeletal muscle while higher levels result in the formation of neurons.