Between Scylla and Charybde: Identification of redundant genes and new markers of embryonic cell fates in Drosophila melanogaster

The output of many signaling cascades is the transcriptional regulation of a diverse set of target genes. In Drosophila, integral components of the signaling pathways that establish embryonic polarity have been isolated genetically. In contrast, the transcriptionally regulated targets of signaling have escaped genetic detection, perhaps due to the difficulty of identifying genes with redundant functions, and genes with highly specialized roles in development through classic genetic methods. These target genes are essential to the understanding of fate specification, as they are the biological “effectors” of signaling. Identification and characterization of these effector targets will reveal how they contribute to the determination of cell fates, and in a broader context will provide insight into the developmental signals conserved among eukaryotes.; New targets of dorsoventral signaling were identified using direct expression screening as a complement to genetic approaches. Three examples illustrate the effectiveness of direct expression screening for the identification of cell fate markers that have previously eluded detection. First, characterization of scylla and charybde revealed a pair of genes with redundant functions that acts to promote a subset of dorsal fates in the embryo. Second, identification of the mesodermal fate marker U5F9 revealed a lipid modification enzyme regulated by the Dorsal signaling pathway, underscoring the biological significance of identifying new effectors of signaling. Third, the characterization of the novel amnioserosa-specific transcript CG12011 provides a link between expression analysis in the early embryo and morphogenetic processes later in development.; Taken together, these data demonstrate the ability to identify a subset of genes that had previously eluded detection. From a biological perspective, the isolation of these new markers of dorsoventral fates will have a tremendous impact on our understanding of the molecular underpinnings of cell fate determination. In a broader context, characterization of downstream effectors of well-characterized signaling pathways will contribute to our knowledge of conserved developmental signals and can be exploited further as model systems in which to study human disease networks.