We have characterised a P-element-induced prepupal mutant of Drosophila melanogaster which after an apparently normal embryonic and larval development fails to complete head eversion, an essential step in metamorphosis. The P-element insertion disrupts an ecdysone-regulated transcript which, although expressed during embryonic and larval stages, appears critical for preparing the late prepupal response to ecdysone. By a combination of molecular and genetic studies, in which we recovered new alleles, we show that the locus is complex, containing at least two distinct promoters. Its transcripts contain a short region described previously by R. Schüh et al. (1986, Cell 47, 1025-1032), who screened for homologues of the Krüppel gene. Our studies on the corresponding gene, named Krüppel-homolog (Kr-h), add to a growing body of evidence that specific isoforms of a number of key genes are implicated in both embryogenesis and metamorphosis.

Gene expression measurements are a powerful tool in molecular biology, but when applied to heterogeneous samples containing more than one cellular type the results are difficult to interpret. We present here a new approach to this problem allowing to deduce the gene expression profile of the various cellular types contained in a set of samples directly from the measurements taken on the whole sample.

Drosophila development is marked by two major morphogenetic processes: embryogenesis and metamorphosis. While insect metamorphosis is known to be controlled by the steroid hormone ecdysone, relatively little is known concerning the hormonal control of embryogenesis. Here we show that many ecdysone-regulated transcripts of metamorphosis are also expressed in a wavelike manner during embryogenesis, suggesting that these genes also participate in an embryonic ecdysone response. At metamorphosis, the Krüppel-homolog (Kr-h) gene, coding for a zinc finger protein, is required during the prepupal ecdysone response. Kr-h mutants die at the prepupal-pupal transition. In these mutants, the expression of several ecdysone-regulated genes is disrupted and we concluded that Kr-h was a key modulator of the hormonal response [Dev. Biol. 221 (2000) 53]. While Kr-h is expressed in many tissues at metamorphosis, in embryos expression is restricted to neurons. Here, we investigate its role during early Drosophila development using new alleles with an earlier lethality than those previously described. Although we detect only minor morphological defects in these mutants, we show that Kr-h expression is necessary for the early development of Drosophila and that, during metamorphosis, Kr-h acts as a modulator of the expression of many of these ecdysone-regulated genes.