Neuronal development in the Drosophila eye disc follows a non-clonal mechanism in which the fate of a neuron is determined by cell-cell interactions. The molecular mechanism underlying the development of the R7 neuron has been studied in some detail and involves a signalling molecule, Boss, and a tyrosine kinase receptor, Sevenless. A new member of this pathway, Son of sevenless (Sos), participates downstream of Sevenless, and is a putative activator of Drosophila Ras1. Experiments are proposed to determine if Sos is a substrate for Sevenless and if Sos directly activates Ras1. A sensitive screening technique to detect new genes possibly belonging to the sevenless pathway is also described. Using this method, a number of genes that affect R7 development have been identified. These will be characterized genetically, and the one most likely to have a direct role in the sevenless pathway will be chosen for molecular characterization. Finally, one gene isolated from the above screen is allelic to Star, which has been previously cloned and sequenced. However, the mechanism by which Star affects neuronal development is unknown. Star functions non-autonomously in specifying the fate of the R7 neuron. Experiments are proposed to evaluate the role of Star in this process of neural induction. The long term goal of this study is to genetically dissect a tyrosine kinase pathway that is involved in the development of photoreceptor neurons. The molecules that belong to this pathway bear striking homology to oncogenes isolated in vertebrates. Thus, a detailed analysis of this pathway could, in the long run, provide insights into mechanisms of neural development in the vertebrate visual system.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY008152-11
Application #
6164668
Study Section
Genetics Study Section (GEN)
Program Officer
Hunter, Chyren
Project Start
1990-01-01
Project End
2002-02-28
Budget Start
2000-03-01
Budget End
2001-02-28
Support Year
11
Fiscal Year
2000
Total Cost
$319,271
Indirect Cost
Name
University of California Los Angeles
Department
Biochemistry
Type
Schools of Arts and Sciences
DUNS #
119132785
City
Los Angeles
State
CA
Country
United States
Zip Code
90095
Wang, Cheng-Wei; Purkayastha, Arunima; Jones, Kevin T et al. (2016) In vivo genetic dissection of tumor growth and the Warburg effect. Elife 5:
Nagaraj, Raghavendra; Gururaja-Rao, Shubha; Jones, Kevin T et al. (2012) Control of mitochondrial structure and function by the Yorkie/YAP oncogenic pathway. Genes Dev 26:2027-37
Mukherjee, T; Choi, I; Banerjee, Utpal (2012) Genetic analysis of fibroblast growth factor signaling in the Drosophila eye. G3 (Bethesda) 2:23-8
Rao, Shubha Gururaja; Banerjee, Utpal (2012) Oncogenic pathway utilizes mitochondrial fusion machinery to support growth. Cell Cycle 11:4491
Freije, William A; Mandal, Sudip; Banerjee, Utpal (2012) Expression profiling of attenuated mitochondrial function identifies retrograde signals in Drosophila. G3 (Bethesda) 2:843-51
Mandal, Sudip; Lindgren, Anne G; Srivastava, Anand S et al. (2011) Mitochondrial function controls proliferation and early differentiation potential of embryonic stem cells. Stem Cells 29:486-95
Yavari, Amir; Nagaraj, Raghavendra; Owusu-Ansah, Edward et al. (2010) Role of lipid metabolism in smoothened derepression in hedgehog signaling. Dev Cell 19:54-65
Mandal, Sudip; Freije, William A; Guptan, Preeta et al. (2010) Metabolic control of G1-S transition: cyclin E degradation by p53-induced activation of the ubiquitin-proteasome system. J Cell Biol 188:473-9
Evans, Cory J; Olson, John M; Ngo, Kathy T et al. (2009) G-TRACE: rapid Gal4-based cell lineage analysis in Drosophila. Nat Methods 6:603-5
Nagaraj, Raghavendra; Banerjee, Utpal (2009) Regulation of Notch and Wingless signalling by phyllopod, a transcriptional target of the EGFR pathway. EMBO J 28:337-46

Showing the most recent 10 out of 32 publications