Spatial and temporal regulation of cell adhesion is mediated by discrete regulatory elements in the delilah locus. Adi Salzberg, Atalya Nachman, Naomi Halachmi, Nirit Egoz-Matia. Gen/Rappaport Fac Medicine, Technion Israel Ins Technology, Haifa, Israel.

   Delilah (Dei) is a transcription factor of the bHLH family that was shown to be an important regulator of cell adhesion in Drosophila. In organs in which sub-groups of cells differentiate into more adhesive and less adhesive cell types, Dei is expressed in the stickier cells, where it is required for inducing PS-integrin expression. In a simplistic way of thinking, Dei can be seen as a molecular switch that turns on PS-integrin expression wherever a sticky cell has to develop. If so, it is predicted that dei, working as a molecular switch which is turned on in different developmental and physiological contexts, would be able to respond to various signaling pathways and transcription factors. Here we show that, as expected, the regulatory region of dei harbors multiple discrete modules that respond to different transcription factors and drive expression in distinct subsets of the dei-expressing cells in different developmental stages. Thus, the dei gene provides a molecular platform through which cell adhesion can be regulated at the transcriptional level. The cis-regulatory modules in the dei locus are scattered along 9.4kb of DNA located upstream to the transcription start site or within the single intron of the gene. Analyses of these regulatory elements revealed new cell types and tissues that express the dei gene. Additionally, the analyses revealed bi-phasic regulation of dei expression in muscles and chordotonal organs and allowed the identification of upstream regulators of dei expression. Further analysis of a specific module that drives expression in attachment cells identified the EGR protein Stripe as a direct regulator of dei and shed light on the common mechanism by which chordotonal attachment cells and tendon cells acquire their unique properties.