The establishment of dorsoventral polarity in the Drosophila embryo has been the subject of extensive genetic, developmental, and biochemical analyses. At least three different signaling pathways are required for proper dorsoventral polarity, two that are under maternal control and a third pathway that requires expression of the genes in the embryo itself. All of these signaling pathways must operate correctly for normal dorsoventral patterning of the embryo.
During oogenesis, the oocyte is surrounded by specialized somatic cells called follicle cells. The follicle cells secrete the various layers of the chorion, or egg shell, during oogenesis. The chorion differs in structure along the dorsoventral axis, showing that the follicle cells have dorsoventral positional information. In addition, the oocyte itself, as well as the resulting embryo, has a dorsoventral polarity. The coordination of dorsoventral polarity between the follicle cells and the growing oocyte involves a signaling pathway of at least 13 different genes and appears to involve signaling from the oocyte to the follicle cells, and then signaling back from the follicle cells to the oocyte (1). That the oocyte sends a dorsalizing signal to the follicle cells is shown by mutations in several genes, including the gurken gene. The gurken gene encodes a transforming growth factor a (TGFa)-like protein that must be expressed in the oocyte in order for the follicle cells to make dorsal chorion structures (2). Loss of gurken function in the oocyte leads to ventralization of the follicle cells. That the follicle cells in turn send a dorsalizing signal is shown by mutations in the torpedo gene. Loss of torpedo function in the follicle cells causes the oocyte (and embryo) to be ventralized (3). The torpedo gene encodes an EGF receptor. Human TGFa has been shown to bind and activate an ectodermal growth factor (EGF) receptor (4), which suggests that torpedo proteins in the follicle cell membranes are receptors for gurken proteins secreted by the oocyte.
Signaling back from the follicle cells to the oocyte involves another pathway that is conserved in the human immune system. This pathway is the dorsal pathway in Drosophila, and it includes at least 12 maternally acting genes (5). Mutations in 11 of these genes cause the oocyte and resulting embryo to be dorsalized. These are the dorsal group of mutations, because they all seem to function to activate the dorsal protein in the embryo (6). The dorsal protein is homologous to the NF-kB/rel proteins required for signaling in the human immune system (7). Mutations in the cactus gene cause the oocyte and embryo to be ventralized. Cactus encodes a homologue of the IkB protein (8), which binds and inhibits NF-kB/rel. Cactus appears to bind and inhibit dorsal in Drosophila (9). The nuclear localization of dorsal protein in the embryo initiates the third signaling pathway in dorsoventral patterning in the Drosophila embryo.
The third signaling pathway required for dorsoventral patterning in the Drosophila embryo is encoded by zygotically active genes, in contrast to the maternal requirements for the first two signaling pathways. This zygotic signaling pathway appears to use the TGFb homologue decapentaplegic (dpp) as the dorsal signal. Loss of dpp activity in the embryo causes ventralization (10). Another TGFb homologue, screw, also appears to be required zygotically for dorsalization of the embryo (11). Dpp and screw may act synergistically in dorsalizing the embryo, because injection of dpp messenger RNA can partially suppress the phenotype of screw mutants, and antimorphic screw mutations enhance loss of dpp activity (11). Three other genes required for dorsalizing the embryo encode homologues of subunits of vertebrate TGFb receptors. These are the genes punt, thick veins, and saxophone (1). Activation of these receptors by the dpp and screw proteins appears to activate transcription of the zerknullt (zen) gene. Zen is a homeobox-containing transcription factor that is required for dorsalization of the embryo (12). Thus, dorsoventral polarity in the Drosophila embryo begins with a signal from the developing oocyte to the follicle cells, a return signal from the follicle cells to the oocyte confirming dorsoventral polarity, and the final activation of at least one transcription factor in dorsal cells of the embryo.
