Reiterative Use of the EGF Receptor Triggers Differentiation of All Cell Types in the Drosophila Eye

Abstract

The Drosophila eye has contributed much to our knowledge of cell differentiation. This understanding has primarily come from the study of the R7 photoreceptor; much less is known about the development of the other classes of photoreceptor or the nonneuronal cone or pigment cells. I have used a dominant-negative form of the Drosophila epidermal growth factor receptor (DER) to show that this receptor tyrosine kinase (RTK) is required for the differentiation of all these cell types, and I have also shown that DER is sufficient to trigger their development. DER is even required in R7, where it can replace Sevenless, another RTK. These results broaden our view of eye development to include the whole ommatidium and suggest that reiterative activation of DER is critical for triggering the differentiation of all cell types.

Identification of the death zone: a spatially restricted region for programmed cell death that sculpts the fly eye

“…Expression of mSpi from single cells in the retina had no effect on retinal patterning (data not shown), consistent with other experiments in which mSpi expressed in the eye was inactive owing to lack of processing. 16,27 In instances where a single lattice cell expressed sSpi, lattice cells multiple cell diameters from the sSpi-expressing cell were rescued from death, as expected from a secreted ligand that moves outward symmetrically in all directions (Figure 5a and b). Note, however, that it is unlikely that sSpi is the spatial regulator as (1) sSpi presumably moves radially outward and (2) experimentally determined levels of P-MAPK (Figure 4) indicate that all lattice cells receive the same level of dEgfr ligand.…”

“…13,19 Conversely, a block in dEgfr signaling leads to ectopic death of lattice cells, whereas hyperactivation of dEgfr signaling rescues all lattice cells from death. [13][14][15][16] As we determined that apoptosis of lattice cells is spatially restricted to the death zone, we hypothesized that we could visualize changes in Notch or dEgfr signaling in lattice cells that are destined to die. Specifically, we expected to see a reduction in dEgfr signaling or an induction of Notch signaling in cells in the death zone regions: horizontal anterior or oblique adjacent to bristle groups.…”

“…We next investigated how blocking of dEgfr signaling in individual cells would affect lattice cell apoptosis. Using the FLP-out technique, a dominant-negative form of dEgfr (DN-dEgfr, 16 ) was expressed in random single cells exclusively during the time of death. Unexpectedly, we observed that individual lattice cells expressing high levels of DN-dEgfr are still able to populate the fully formed lattice (Figure 6a-c).…”

“…7 In contrast to PCD in Caenorhabditis elegans, lattice cell death is not specified by lineage; therefore, cell death in the developing Drosophila retina must be directed by positional information through cell-cell communication, 11,12 as is also the case in mammalian development. Several laboratories have demonstrated that signaling from the Drosophila epidermal growth factor receptor (dEgfr/ DER/Torpedo/Flb)/ras pathway promotes lattice cell life, [13][14][15][16] in part through negative regulation of the cell death effector head involution defective (HID). 17,18 During the period of lattice cell death, dEgfr is expressed by all lattice cells, and its soluble ligand, Spitz (Spi), is expressed by cone cells and primary pigment cells.…”

Transgene‐mediated RNA interference defines a novel role for notch in chemosensory startle behavior

“…Using the drivers Sev-Gal4 (Fortini et al, 1993) and GMR-Gal4 (Freeman, 1996), we expressed the transgene in cells in the eye imaginal disc posterior to the morphogenic furrow. It is well established that Notch is required for successive cell fate decisions in the developing Drosophila retina (Cagan and Ready, 1989), and disruption in Notch signaling leads to disorganizations of the ommatida and a roughening of the eye.…”