Regulation and determination of cell fate are fundamental to development. Identification of selector genes in Drosophila allows description of these elusive phenomena in terms of gene expression. Expression of a particular selector gene selects a particular pathway of development. Selector gene expression must change when cells change their fate in response to environment (regulation), whereas selector gene expression must be stably maintained when a cell and its progeny are committed to a pathway of development (determined). Expression of engrailed, a selector gene, commits cells to the posterior compartment of a segment, but expression is not initially stable. Cell-cell signalling in very young embryos appears to represent regulative control of engrailed expression. Subsequently, engrailed expression appears to be stabilized as it comes under the influence of two later tiers of control. As a paradigm for the processes of regulation and determination, Dr. O'Farrell is examining engrailed expression. He will define when and where determination of engrailed expression occurs. He will explore the involvement of autoregulation and candidate "maintenance genes" in the stabilization of engrailed expression. He will map engrailed regulatory sequences that mediate regulative and determinative programs of expression. From this base he will study the molecular mechanisms of regulation and determination in development.
