| Dip3 is a member of the MADF-BESS domain transcription factor family, members of which are found in both invertebrates and vertebrates. This protein family possesses a unique architecture, containing both a DNA binding domain, the MADF domain, and an activation domain, the BESS domain. However, the function of this transcription factor family is largely unknown. Here I show that Dip3 is essential in eye development. Its expression in photoreceptors triggers a signal that leads a sub-population of undifferentiated cells to adopt appropriate non-neuronal fates. Loss of Dip3 function results in the addition of an extra photoreceptor to each ommatidium, while over-expression of Dip3 results in photoreceptor loss, but promotes the formation of extra cone and primary pigment cells. I further showed that Dip3 regulates cell fate determination most likely by modulating Notch signaling. The Dip3 over-expression phenotype is significantly suppressed by reducing of the Notch gene dosage to one, or enhanced by co-expressing Dip3 with Dl, a Notch ligand. Furthermore, misexpression of Dip3 leads to ectopic expression of E(spl), a well-known Notch response gene. Consistent with the role for Dip3 in triggering Notch signaling, the Dip3 loss-of-function phenotype is similar to the phenotype previously reported for an eye specific allele of the Notch pathway component groucho (gro). The identification of four point mutations that inactivate Dip3 function, and that all map to the MADF domain, suggests that the Dip3 MADF domain is required for patterning of the retina.;I also show here that Dip3 alters fate determination when misexpressed in the early eye-antennal disc, and have taken advantage of this observation to gain new insight into the mechanisms controlling the eye-antennal switch. Dip3 misexpression yields extra antennae by two distinct mechanisms: the splitting of the antennal field into multiple antennal domains (antennal duplication), and the transformation of the eye disc to an antennal fate. Antennal duplication requires Dip3-induced under proliferation of the eye disc and concurrent over proliferation of the antennal disc. While previous studies have shown that overgrowth of the antennal disc can lead to antennal duplication, my results show that overgrowth is not sufficient for antennal duplication, which may require additional signals perhaps from the eye disc. Eye-to-antennal transformation appears to result from the combination of antennal selector gene activation, eye determination gene repression, and cell cycle perturbation in the eye disc. Both antennal duplication and eye-to-antennal transformation are suppressed by the expression of genes that drive the cell cycle providing support for tight coupling of cell fate determination and cell cycle control. The finding that this transformation occurs only in the eye disc, and not in other imaginal discs, suggests a close developmental and therefore evolutionary relationship between eyes and antennae. |
