Figure 4. Interaction events governing expression of the eve gene.

Direct and indirect interactions are shown in solid and dashed lines, respectively. Protein factors are shown as circles; genes are represented as boxes. A. The specification of future eve expression is mediated by the Dpp signaling that activates Smad effectors (Mad and Medea) that oligomerize and positively control tin expression. In parallel, Wg signaling stabilizes the transcription activator Arm and promotes its formation of a complex with the DNAbinding factor Pan and releasing it from a transcription repressor (not shown). Dpp and Wg specify the location of future eve expression as their contribution is equally important and thereby eve activation can be achieved only at Dpp and Wg signals intersection zones (see Fig.1 C'); the tin gene is active only in the mesoderm and thereby provides the mesodermal context to eve activation. However, the activity of the transcriptional repressor Anterior open (Aop) puts eve expression on hold (yellow shading). B. Within the cardiac mesoderm, a local activation of the receptor Htl by Pyr or Ths ligands subsequently leads to activation of the MAPK pathway, attendant activation of the transcription factor Pnt, and inactivation of the repressor Aop. The cooperative stimulatory inputs activate eve transcription (green) in small clusters of cardiac mesoderm. C. The final process of singling out a progenitor cell (left side) from adjacent neighboring cells (right side) within a cluster of eve-expressing cells. In the progenitor, the active RTK signaling pathway activates expression of the eve marker gene along with components of the Notch signal: the receptor Notch (N) and its ligand Delta (Dl). Here, the components of the RTK signaling, Htl and Hbr, are also self-maintained, while the Notch receptors are not active (shown in subdued colors) in the absence of Delta received from the neighboring cells. In contrast, neighboring cells receive the Delta signal produced by the progenitor cell, which leads to activation of N and suppression of the RTK signaling (subdued) and most of its targets, including the eve and Delta genes. Meanwhile, the Notch receptor stimulates its own expression to maintain and amplify the N signal. The neighboring cell cannot activate N signaling in the progenitor cell, as its own Delta production is suppressed by active Notch.