The objective of this research is to understand the development of the visual system and retina and, in particular, precursor cells specified to particular fates. To address these issues, the investigator proposes to study the regulation of the ERK, a central molecule in the machinery used by all cells to interpret developmental signals. The inactive form of ERK is a cytoplasmic protein, where it exists in association with its own specific activating kinase, MEK, and the cells' microtubule skeleton. Signals from many sources can cause MEK to activate ERK. These signals include those from tyrosine kinases and other receptors. The active form of ERK is called dp-ERK, which has been thought to move immediately to the cell nucleus where it can act on transcription factors to control gene expression. In the developing retina, ERK signaling is regulated by receptor tyrosine kinases that include the EGF receptor. This pathway allows extracellular signals (such as growth factors) to affect retinal cell development. The investigator has found that Drosophila dp-ERK does not immediately move to the nucleus. Instead it is held in the cytoplasm until it is released by signals from a second pathway controlled by the Notch receptor. Notch is known to act in local signaling between contacting cells, including those in the developing retina. Thus, the investigator proposes that these two pathways interact to control retinal cell fate in Drosophila. As both pathways are known to act also in vertebrate retinal development, this novel aspect of regulation may be general. The investigator proposes to study Notch-regulated ERK cytoplasmic hold (CH) in both Drosophila and rats.
The specific aims are focused on uncovering the biochemical mechanism by which this occurs.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY012537-02
Application #
6179076
Study Section
Visual Sciences C Study Section (VISC)
Program Officer
Hunter, Chyren
Project Start
1999-05-03
Project End
2003-04-30
Budget Start
2000-05-01
Budget End
2001-04-30
Support Year
2
Fiscal Year
2000
Total Cost
$268,609
Indirect Cost
Name
Emory University
Department
Anatomy/Cell Biology
Type
Schools of Medicine
DUNS #
042250712
City
Atlanta
State
GA
Country
United States
Zip Code
30322
Jones, Chonnettia; Reifegerste, Rita; Moses, Kevin (2006) Characterization of Drosophila mini-me, a gene required for cell proliferation and survival. Genetics 173:793-808
Vrailas, Alysia D; Moses, Kevin (2006) Smoothened, thickveins and the genetic control of cell cycle and cell fate in the developing Drosophila eye. Mech Dev 123:151-65
Marenda, Daniel R; Vrailas, Alysia D; Rodrigues, Aloma B et al. (2006) MAP kinase subcellular localization controls both pattern and proliferation in the developing Drosophila wing. Development 133:43-51
Vrailas, Alysia D; Marenda, Daniel R; Cook, Summer E et al. (2006) smoothened and thickveins regulate Moleskin/Importin 7-mediated MAP kinase signaling in the developing Drosophila eye. Development 133:1485-94
Rodrigues, Aloma B; Werner, Erica; Moses, Kevin (2005) Genetic and biochemical analysis of the role of Egfr in the morphogenetic furrow of the developing Drosophila eye. Development 132:4697-707
Jones, Chonnettia; Moses, Kevin (2004) Cell-cycle regulation and cell-type specification in the developing Drosophila compound eye. Semin Cell Dev Biol 15:75-81
Kumar, Justin P; Hsiung, Frank; Powers, Maureen A et al. (2003) Nuclear translocation of activated MAP kinase is developmentally regulated in the developing Drosophila eye. Development 130:3703-14
Hsiung, Frank; Moses, Kevin (2002) Retinal development in Drosophila: specifying the first neuron. Hum Mol Genet 11:1207-14
Kumar, J P; Moses, K (2001) Expression of evolutionarily conserved eye specification genes during Drosophila embryogenesis. Dev Genes Evol 211:406-14
Kumar, J P; Moses, K (2001) The EGF receptor and notch signaling pathways control the initiation of the morphogenetic furrow during Drosophila eye development. Development 128:2689-97

Showing the most recent 10 out of 13 publications