Characterization ofbicaudal, a maternal effect mutation of Drosophila melanogaster

The Drosophila melanogaster mutation bicaudal (bic) is the founding member of the group of maternal effect mutations that disrupt anterior-posterior axis formation by creating mirror image duplications of posterior segments in the anterior half of the embryo. The gene affected by the bic mutation was cloned, and a recessive embryonic lethal mutation, $vr22\sp{P3},$ was shown to be an allele of the same gene, demonstrating that the gene is essential. During embryogenesis, bic gene expression was detected in mesoderm and anterior and posterior midgut, and persistent expression was found in the somatic musculature. Late in embryogenesis, transcripts were detected in the central nervous system. The bic gene was shown to be expressed in two distinct locations in ovaries: transcripts were detected in somatic cells of the germarium, and a second activation of transcription was found exclusively in the germ-line derived nurse cells of ovarian follicles. The maternal effect of the bic mutation was shown to originate in failure to express transcripts of the gene in the germ-line nurse cells during oogenesis. The bic gene was found to encode the Drosophila homolog of beta NAC (Nascent polypeptide Associated Complex), a recently discovered ribosome associated protein of eukaryotes. Beta NAC is a subunit of a heterodimer that associates with nascent polypeptides as they emerge from the ribosome. In vitro, NAC regulates the specificity of co-translational targeting of nascent chains to the Endoplasmic Reticulum. The studies of the bic mutant effects presented here demonstrated that beta NAC has other unpredicted ribosome-associated functions, being required to ensure localized expression of proteins via translational control of mRNA. In oocytes/embryos of bic mutant females, negative regulation of translation of the mRNA of nanos, the posterior determinant, fails; NANOS protein is aberrantly expressed in the anterior compartment of the early embryo, and consequently, bicaudal embryos are created. Negative regulation of nanos was thus shown to include ribosome associated events. Furthermore, these first in vivo studies of the activity of beta NAC (BIC) identified a new ribosome associated function for the protein, and established a physiologically relevant and informative molecular genetic model system for future studies of NAC