Salivary gland determination in drosophila: A salivary-specific, fork headenhancer integrates spatial pattern and allows fork head autoregulation

In the early Drosophila embryo, a system of coordinates is laid down by seg mentation genes and dorsoventral patterning genes. Subsequently, these coor dinates must be interpreted to define particular tissues and organs. To beg in understanding this process for a single organ, we have studied how one o f the first salivary gland genes, fork head (fkh), is turned on in the prim ordium of this organ, the salivary placode. A placode-specific fkh enhancer was identified 10 kb from the coding sequence. Dissection of this enhancer showed that the apparently homogeneous placode is actually composed of at least four overlapping domains. These domains appear to be developmentally important because they predict the order of salivary invagination, are evol utionarily conserved, and are regulated by patterning genes that are import ant for salivary development. Three dorsoventral domains are defined by EGF receptor (EGFR) signaling, while stripes located at the anterior and poste rior edges of the placode depend on wingless signaling. Further analysis id entified sites in the enhancer that respond either positively to the primar y activator of salivary gland genes, SEX COMBS REDUCED (SCR), or negatively to EGFR signaling. These results show that fkh integrates spatial pattern directly, without reference to other early salivary gland genes. In additio n, we identified a binding site for FKH protein that appears to act in fkh autoregulation, keeping the gene active after SCR has disappeared from the placode. This autoregulation may explain how the salivary gland maintains i ts identity after the organ is established. Although the fkh enhancer integ rates information needed to define the salivary placode, and although fkh m utants have the most extreme effects on salivary gland development thus far described, we argue that fkh is not a selector gene for salivary gland dev elopment and that there is no master, salivary gland selector gene. Instead , several genes independently sense spatial information and cooperate to de fine the salivary placode. (C) 2001 Academic Press.