Control of expression of the homeotic labial (lab) locus of Drosophila melanogaster: evidence for both positive and negative autogenous regulation

Abstract

The homeotic gene labial (lab) is required for proper development of the embryonic and adult head in Drosophila melanogaster. The lab gene product accumulates in a complex pattern in both embryonic and imaginal tissue. During embryogenesis, lab is expressed in the endodermally derived cells of the midgut, in ectodermally derived cells of the procephalon and dorsal ridge, and in a small subset of progenitor sensory cells. Imaginal expression is restricted to a narrow region of the peripodial membrane of the eye-antennal disc. As part of our continuing effort to understand the role of lab in development, we have begun a dissection of the regulatory elements of the lab transcription unit and used germ line transformation experiments to determine which aspects of the observed expression pattern are essential for proper head development and viability. Transgenic embryos harboring an abridged lab gene are able to overcome the embryonic lethality associated with the loss of lab function and survive to adulthood. Interestingly, in these transgenic lines the lab protein accumulates only in a subset of those embryonic cells that normally express the gene, namely the procephalon and the anterior midgut. We also find that, once initiated, lab expression is maintained by positive autoregulation. Although lab minigene activity is sufficient to rescue the embryonic lethality of lab mutations, the transgenes fail to rescue defects in the adult head capsule. However, the defects observed in this study encompass a broader domain than those seen using somatic recombination to generate lab- clonal tissue. The failed rescue and observed cuticular defects are, at least in part, explained by the observation that the transgenes, rather than failing to be expressed, are associated with ectopic accumulation of lab protein in the peripodial membrane of the antennal disc. Moreover, this aberrant expression pattern is correlated with the abnormal expression of two other homeotic genes, Deformed (Dfd) and Sex combs reduced (Scr) in the eye-antennal disc. These results are only observed when the transgene is resident in a lab- genotype and ectopic expression of lab and misregulation of Dfd and Scr are not seen in a lab+ background. This result suggests that the wild-type lab gene product is necessary for the normal regulation of the locus in the imaginal discs, but unlike the case in the embryo, the event is negative. We discuss the biological implications of these results in relation to the role of lab in development.