Homeobox Genes DataBase

Drosophila Genes in Development: Dorsal-ventral and Anterior-posterior patterning

Dorsal

Function

Dorsal is the focal protein in the development of dorsoventral polarity in the developing fly. It is a transcription factor, activating and repressing zygotic genes responsible for differentiation along the dorsoventral axis during the early stages of development. Over the course of time measured in hours, even before cellularization, the rapidly dividing zygotic cells take up their positions at the periphery of the fertilized egg. Nuclei in the ventral portion stain positive for DL while nuclei in the dorsal region fail to stain. Nuclear staining is graded; nuclei closest to the ventral midline stain most strongly (Rushlow C., 1989, Steward R., 1989 and Roth S., 1989).

The dorsal group comprises a whole class of genes acting in the mother and responsible for setting up the activation and nuclear transport of DL. The polarization of the egg early in oogenesis affects the follicle cells surrounding the egg. Ventral follicle cells take on a different developmental fate from dorsal follicle cells. For example, the release and activation of the Toll ligand SpДtzle occurs only in the ventral region of the egg. Once fertilization has taken place, SpДtzle triggers signaling in the Toll receptor. The signals are transmitted via Tube and Pelle into the cytoplasm, resulting in the activation of Dorsal. Cactus protein binds Dorsal, preventing its nuclear transport. Signals from Toll result in the destruction of Cactus in ventral cells, whereupon Dorsal is released to continue its transportation into the nucleus.

In the immune system of the adult fly bacterial challenge causes the activation of Dorsal and a second Dorsal-like factor (Dif) in the fat body, an organ that serves the immune function in flies. The developing awareness of the importance of an immune response system in flies has initiated a new focus of interest in Dorsal research (Reichart J. M., 1993 and Lemaitre B., 1995).

Cell fate along the dorsoventral (DV) axis in early Drosophila melanogaster development is determined by the activity of several zygotic genes whose localized expression is regulated by the dorsal (dl) transcription factor. Initially, the dorsal protein (DL) is uniformly distributed in the cytoplasm of the egg cell. After fertilization, during cleavage cycle 10 and until cycle 14, DL is transported from the cytoplasm into the nuclei in a regulated manner such that ventral nuclei receive high levels of DL while lateral and dorsal nuclei receive progressively decreasing amounts of DL. This regulation involves a signal transduction pathway involving maternal factors that trigger the asymmetric movement of DL into nuclei. As a result, a nuclear concentration gradient of DL forms, with the highest concentration in ventral nuclei. DL can thus be described as a maternal morphogen, because it acts in a concentration-dependent manner to set up distinct patterns of zygotic gene expression along the DV axis.

Genes such as twist (twi) and snail (sna) are activated by high concentrations of DL in ventral nuclei, where they direct the formation of the mesoderm. In lateral regions of the embryo, intermediate amounts of DL can turn on genes, such as rhomboid (rho), which are involved in the formation of the neuroectoderm. DL is also believed to repress the transcription of a set of genes responsible for the differentiation of dorsal tissues.

A number of DL binding sites have been found in promoter regions of the activated genes twi, sna and rho. In most cases, they are clustered in regions which are saturated with binding sites for other transcription factors, implying that a complex set of short-range interactions mediates the spatially restricted expression patterns.

zerknullt (zen), decapentaplegic (dpp), tolloid (tld): transcription of these genes is initiated during cleavage cycle 10 at about the same time as when DL enters nuclei in ventral regions of the embryo. They transcripts appear only in the dorsal half of the embryo and are never seen in ventral regions. It is thought that DL restricts their expression by preventing expression in ventral nuclei.

DL is by default an activator and works as a repressor only in specific promoter contexts.

The adult fly uses the identical system in its immune system. Bacterial challenge causes the activation of Dorsal and a second Dorsal-like factor (Dif) in the fat body, an organ that serves the immune function in flies. The developing awareness of the importance of an immune response system in flies has initiated a new focus of interest in Dorsal research (Reichart J. M., 1993 and Lemaitre B., 1995).

Protein

DL is a sequence-specific DNA binding protein that shows homology to the Re1 family of transcription factors.

The Dorsal protein has a large N-terminal region of 294 amino acids, homologous to the vertebrate c-rel and its corresponding viral oncogene V-rel, the transforming gene of the reticuloendotheliosis virus strain T (Steward R., 1987). The C-terminal divergent half of Dorsal is dispensable for its selective nuclear import. A basic stretch of 6 amino acids at the C terminus of the Rel-homology region is necessary for nuclear localization (Govind S., 1996).

Subcellular location

Nuclear and cytoplasmic

Expression Pattern

Stage 10 egg chambers show a strong DL protein staining in nurse cells. Dorsal is transported into the oocyte by a cytoskeletal based mechanim later when nurse cell contents are distributed to the oocyte (Rushlow C., 1989). After fertilization there is a graded nuclear localization of DL protein. The ventral region of the embryo shows complete nuclear transport, the lateral portion shows intermediate transport and the dorsal portion shows no transport. In the absence of Cactus function, the DL protein is found in nuclei on the dorsal as well as the ventral side (Roth S., 1989). In mutants of the dorsal group of genes, including easter, spДtzle and Toll, no nuclear localization is observed (Steward R., 1989).

Even before cellularization, nuclei in the ventral part of the early embryo stain positive for DL while nuclei in the dorsal region fail to stain. Nuclear staining is graded; nuclei closest to the ventral midline stain most strongly (Rushlow C., 1989, Steward R., 1989 and Roth S., 1989).

DL activates CAT expression from a zen-CAT construct. CAT activity is enhanced in the presence of either TL or Pka-C1. Both Tl and Pka-C1 proteins affect DL nuclear localization and DL activity in the nucleus. Evidence suggests that the signalling pathway from TL to DL acts through Pka-C1. dl mutant constructs were tested to map the regions of dl required for responses to TL and Pka-C1. (Norris J.L., 1992)