Morphogenesis of the insect kidney, the Malpighian tubules, is controlled in Drosophila by a single large cell, the tip cell. It has been postulated that this cell sends out a mitogenic signal that induces the division of neighboring cells. The signal and the molecules that receive it have remained elusive. We show that the COUP-TF-related nuclear orphan receptor Seven-up is a key component that becomes induced in response to mitogenic EGF receptor signaling activity emanating from the tip cell. Seven-up in turn is capable of regulating the transcription of cell cycle regulators.

Irregular facets (If ) is a dominant mutation of Drosophila that results in small eyes with fused ommatidia. Previous results showed that the gene Krüppel (Kr), which is best known for its early segmentation function, is expressed ectopically in If mutant eye discs. However, it was not known whether ectopic Kr activity is either the cause or the result of the If mutation. Here, we show that If is a gain-of-function allele of Kr. We then used the If mutation in a genetic screen to identify dominant enhancers and suppressors of Kr activity on the third chromosome. Of 30 identified Kr-interacting loci, two were cloned, and we examined whether they also represent components of a natural Kr-dependent developmental pathway of the embryo. We show that the two genes, eyelid (eld) and extramacrochaetae (emc), which encode a Bright family-type DNA binding protein and a helix-loop-helix factor, respectively, are necessary to achieve the singling-out of a unique Kr-expressing cell during the development of the Malpighian tubules, the excretory organs of the f ly. The results indicate that the Kr gain-of-function mutation If provides a tool to identify genes that are active during eye development and that a number of them function also in the control of Kr-dependent developmental processes.

The F elements of Drosophila melanogaster belong to the superfamily of long interspersed nucleotide element retrotransposons. To date, F-element transcription has not been detected in flies. Here we describe the isolation of a member of the F-element family, termed Fex, which is transcribed in specific cells of the female and male germ lines and in various tissues during embryogenesis of D. melanogaster. Sequence analysis revealed that this element contains two complete open reading frames coding for a putative nucleic acidbinding protein and a putative reverse transcriptase. Functional analysis of the 5 region, using germ line transformation of Fex-lacZ reporter gene constructs, demonstrates that major aspects of tissue-specific Fex expression are controlled by internal cis-acting elements that lie in the putative coding region of open reading frame 1. These sequences mediate dynamic gene expression in eight expression domains during embryonic and germ line development. The capacity of the cis-regulatory region of the Fex element to mediate such complex expression patterns is unique among members of the long interspersed nucleotide element superfamily of retrotransposons and is reminiscent of regulatory regions of developmental control genes.