Combinatorial patterning mechanisms in the Drosophila embryo

The classical concept of the morphogen gradient proposes that small differences in the levels of a signalling molecule or transcription factor are responsible for producing a continuous spectrum of distinctive cellular identities across a naïve field of cells. In this review, we discuss how the Dorsal gradient controls the dorsal-ventral patterning of the early Drosophila embryo. This gradient extends from the ventral midline of the embryo into dorso-lateral regions, encompassing a cross-sectional field of approximately 20 cells. There is no evidence that these cells acquire distinctive identities due to subtle changes in the nuclear concentrations of the Dorsal protein. Rather, a variety of evidence suggests that the Dorsal gradient generates just three primary thresholds of gene activity. High levels activate gene expression in the presumptive mesoderm, while intermediate and low levels activate gene expression in the ventral and dorsal neurogenic ectoderm, respectively. We discuss how these primary readouts of the gradient establish localized domains of cell signalling, which work in a combinatorial manner with transcriptional networks to produce complex patterns of gene expression and tissue differentiation.