A new family of growth factors produced by the fat body and active on Drosophila imaginal disc cells.

By fractionating conditioned medium (CM) from Drosophila imaginal disc cell cultures, we have identified a family of Imaginal Disc Growth Factors (IDGFs), which are the first polypeptide growth factors to be reported from invertebrates. The active fraction from CM, as well as recombinant IDGFs, cooperate with insulin to stimulate the proliferation, polarization and motility of imaginal disc cells. The IDGF family in Drosophila includes at least five members, three of which are encoded by three genes in a tight cluster. The proteins are structurally related to chitinases, but they show an amino acid substitution that is known to abrogate catalytic activity. It therefore seems likely that they have evolved from chitinases but acquired a new growth-promoting function. The IDGF genes are expressed most strongly in the embryonic yolk cells and in the fat body of the embryo and larva. The predicted molecular structure, expression patterns, and mitogenic activity of these proteins suggest that they are secreted and transported to target tissues via the hemolymph. However, the genes are also expressed in embryonic epithelia in association with invagination movements, so the proteins may have local as well as systemic functions. Similar proteins are found in mammals and may constitute a novel class of growth factors.

Needs and targets for the multi sex combs gene product in Drosophila melanogaster.

We have analyzed the requirements for the multi sex combs (mxc) gene during development to gain further insight into the mechanisms and developmental processes that depend on the important trans-regulators forming the Polycomb group (PcG) in Drosophila melanogaster. mxc is allelic with the tumor suppressor locus lethal (1) malignant blood neoplasm (l(1)mbn). We show that the mxc product is dramatically needed in most tissues because its loss leads to cell death after a few divisions. mxc has also a strong maternal effect. We find that hypomorphic mxc mutations enhance other PcG gene mutant phenotypes and cause ectopic expression of homeotic genes, confirming that PcG products are cooperatively involved in repression of selector genes outside their normal expression domains. We also demonstrate that the mxc product is needed for imaginal head specification, through regulation of the ANT-C gene Deformed. Our analysis reveals that mxc is involved in the maternal control of early zygotic gap gene expression previously reported for some PcG genes and suggests that the mechanism of this early PcG function could be different from the PcG-mediated regulation of homeotic selector genes later in development. We discuss these data in view of the numerous functions of PcG genes during development.

Transposon-induced rearrangements in the duplicated locus ph of Drosophila melanogaster can create new chimeric genes functionally identical to the wild type.

Variation in the number of gene copies can play a major role in changing the coding capacities of eukaryotic genomes. Different mechanisms, such as unequal recombination or transposon-induced chromosome rearrangements, are believed to be responsible for these events. We have used the direct tandem duplication at the complex locus polyhomeotic (ph) of Drosophila melanogaster as a model system to study functional redundancy associated with chromosomal rearrangements, such as duplications or deletions. The locus covers 28.6 kb and comprises two independent units, ph proximal and ph distal, which are not only similar on the molecular level, but appear to be functionally redundant [Dura et al., Cell 51 (1987) 829-839; Deatrick et al., Gene 105 (1991) 185-195]. We present a molecular and phenotypic analysis of two hypomorphic ph mutants, ph2 and ph4, induced during hybrid dysgenesis. Each corresponds to an internal deletion in the ph locus that overlaps both transcription units. We show that the deletions are likely due to a P/M hybrid dysgenesis-induced rearrangement between proximal and distal ph, that created a single new chimerical ph gene. At least one of the breakpoints must be located in a 1247-bp region that is rich in single sequence, and 100% identical between proximal and distal ph. Junction points between units are in the protein-coding regions, but could not be exactly localized on the genomic sequence of either mutant, because of the precise molecular mechanism that caused the deletions. Protein products of the hybrid genes contain the same functional domains as either wild-type (wt) product.(ABSTRACT TRUNCATED AT 250 WORDS)

A regulatory function for K10 in the establishment of dorsoventral polarity in the Drosophila egg and embryo.

Several lines of evidence suggest that the origin of pattern formation of Drosophila embryos must be traced back to oogenesis, to the polarity of the egg chamber. A few early-acting genes, K10, top, grk and cni, have been identified which are assumed to function in a signal transduction process between the germline oocyte and the somatic follicle cells, during which the egg chamber acquires a dorsoventral polarity. K10 has been cloned and was shown to encode a putative transcription factor specifically acting in the oocyte nucleus. In order to characterize further the function of K10, we have analyzed its genetic interactions with grk, top and cni. We show that grk behaves as a dominant partial suppressor of K10. Analysis of the rescuing process of the K10 phenotype by grk shows that: (1) K10 is not indispensable for the establishment of dorsoventral polarity of the egg chamber, since its lack of function can be compensated for by reducing the grk wild-type copy number; (2) grk function is highly dose-sensitive; (3) the rescue process shows an anteroposterior effect suggesting that K10 may also interact with genes involved in anteroposterior pattern formation. These results are compatible with a model in which grk is a dorsalizing signal emanating from the oocyte nucleus, whose level of expression is regulated negatively by the K10 product.