Research Interests

My associates and I have sought to understand how crude gradients of regulatory factors produce sharp on/off patterns of gene expression in the precellular embryo of the fruitfly, Drosphila melanogaster. A twofold difference in the levels of the maternal dorsal gradient determines whether a naive embryonic cell follows a mesodermal or neuronal pathway of differentiation. A similar change in the bicoid gradient localizes a segmentation stripe of eve expression at the boundary between the presumptive head and thorax. The analysis of bicoid and dorsal target genes suggest that complex enhancers, containing clustered binding sites for both transcriptional activators and repressors, are responsible for converting these maternal gradients into localized stripes, bands, and tissue-specific patterns of gene expression. In principle, short-range repressors can account for composite patterns of gene expression such as multiple eve stripes, whereby different enhancers work independently of one another within the same promoter region. Recent studies suggest that a common corepressor protein, dCtBP, is employed by a variety of different short-range repressors.

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Section 22: Cellular and Developmental Biology