TWINS, THE B/PR55 REGULATORY SUBUNIT OF PROTEIN PHOSPHATASE IIA, IS NECESSARY FOR PHOTORECEPTOR FATE SPECIFICATION AND MORPHOGENETIC FURROW INITIATION IN THE DROSOPHILA MELANOGASTER EYE
Bissonnette, Dennis Michael
The Ras/MAPK pathway plays an essential role in the development and differentiation of eukaryotic organs. During Drosophila eye development, the cells of each unit, or ommatidium, of the eye are specified from a field of undifferentiated cells. As the morphogenetic furrow passes across the eye field, the Ras/MAPK pathway is reiteratively activated in cells posterior to the furrow to recruit first the eight photoreceptors, then the four cone cells, and finally the pigment cells. Understanding Ras/MAPK?s regulation is essential to knowing how its activation can generate so many cellular outcomes. The enzyme protein phosphatase 2A (PP2A) is critical for successfully transducing the Ras/MAPK signal. PP2A is composed of three subunits, the associated A and catalytic C subunits compose the core enzyme, and a variable B subunit which regulates the activity of the enzyme. The Drosophila gene twins encodes the B/PR55 regulatory subunit of PP2A. Mutations in twins have previously been shown to affect the development of peripheral sensory organs in the adult fly. Large patches of mechanosensory organs are missing from the thorax of the fly, while those that remain have duplicated bristles and sockets at the expense of the mechanosensors? neuron and sheath cells. Additionally, notal tissue is sometimes transformed to wing at the posterior edges of the notum. To better understand the role of twins in Ras/MAPK signaling during eye development, a genetic approach utilizing loss of function mutants and ectopic twins expression was used. Hypomorphic twins mutants were missing R7 photoreceptors, cone cells, and had disorganized pigment cells. Furthermore, these twins mutations were found to suppress the egfrE1 mutation, a hypermorphic allele of the Ras/MAPK receptor EGFR. Ectopic expression of twins was able to rescue the morphogenetic furrow inhibition caused by loss of EGFR function, suggesting that twins functions downstream of EGFR in Ras/MAPK signalling. Additionally, twins suppressed furrow inhibition caused by ectopic wg, but not that caused by the loss of Notch activation, supporting twins role in regulating Ras/MAPK positively. These results suggest that twins is a positive regulator of Ras/MAPK, necessary for a subset of Ras/MAPK dependent ommatidial developmental events.
twins, PP2A, EGFR, Ras, Drosophila
dissertation or thesis