Mutations in the Drosophila gene extradenticle affect the way specific homeo domain proteins regulate segmental identity.

Abstract

We characterized a gene, extradenticle, which seems to interact with a specific subset of Drosophila homeo domain proteins, possibly affecting their target specificity. This interpretation is based on an examination of the zygotic and maternal effect phenotypes of extradenticle mutations. In embryos with reduced levels of extradenticle gene product, anterior and posterior segmental transformations occur. Segmental identity in Drosophila is mediated by the products of the Antennapedia and bithorax complexes. These homeo domain proteins are thought to regulate different target genes specifically in each segment, resulting in different morphologies, extradenticle alters segmental identity without affecting the pattern of expression of homeotic genes. Genetic tests demonstrate that in extradenticle mutants, the homeotic proteins are functional and act in their normal segmental domains, yet segmental identities are altered. Even when homeotic proteins are ectopically expressed under the control of a heterologous promoter, extradenticle mutations affect their consequences. Thus, in the absence of sufficient extradenticle product, altered segmental morphology results from alteration of the functional consequences of specific borneo domain proteins, possibly through alterations in their target gene specificity, extradenticle is also expressed maternally. Complete removal of extradenticle, maternally and zygotically, leads to specific alterations in segmentation, many of which result from failure to maintain the expression of the homeo domain protein engrailed.

Functional and regulatory interactions between Hox andextradenticle genes

“…7C). This segment pattern resembles closely that found in the A1 segment of zygotic exd − larvae and is the same overall pattern observed after heat shock-inducing Ubx expression in zygotic exd − embryos (Peifer and Wieschaus 1990). These observations indicate that high levels of Ubx protein are able to produce an exd-like phenotype, in good agreement with the observed negative effect of BX-C genes on the nuclear translocation of Exd.…”

“…1D) and the pattern of cells that do so is similar or identical to the wild type. This suggests that the protein translated from maternal RNA is functional, a result that is consistent with experiments showing that the presence of extra copies of the exd gene during oogenesis can rescue the exd zygotic phenotype (Peifer and Wieschaus 1990). It also indicates that regulation of protein distribution is not dependent on transcriptional control.…”

“…In the presence of normal exd function, Ubx specifies the pattern of the first abdominal (Al) segment. In contrast, in embryos lacking exd function, Ubx specifies a pattern resembling a more posterior segment, of A3-A5 type (Peifer and Wieschaus 1990).…”

“…Mutations in exd alter the identity of some body segments without altering the expression pattern of the homeotic genes (Peifer and Wieschaus 1990;Rauskolb et al 1993). The Exd protein contains a homeodomain and acts as a cofactor of the homeotic proteins; in vitro binding experiments have also shown that Exd can cooperatively bind to DNA with the Ultrabithorax (Ubx) and Abdominal-A (Abd-A) proteins, increasing their affinity for some target sites (Chan et al 1994;van Djik and Murre 1994).…”

Meis Proteins are Major In Vivo DNA Binding Partners for Wild-Type but Not Chimeric Pbx Proteins

“…In Drosophila melanogaster, exd is required for the execution of genetic programs that are also dependent on Hox proteins for appropriate segment-specific expression (40,45,46). A similar role for mammalian Pbx proteins is suggested by genetic analyses demonstrating that sequence elements with features of Pbx-Hox consensus sites are required for appropriate expression of murine Hoxb-1 in the developing hindbrain (44).…”