The developmental mutants of Drosophila melanogaster have proven to be a rich and productive area of study for investigations into basic mechanisms in development. We have chosen one such genetic locus, engrailed for intensive study. Our work and the work of others has shown that the engrailed locus is essential in normal morphogenesis of all of the developing segments of Drosophila and that this requirement is restricted to the cells of the posterior compartment in each segment. Our work has more recently revealed that the locus is extremely large and complex: engrailed mutations define a region that exceeds 70,000 base pairs, interactions between different mutant alleles are complex, and the RNA transcripts that the locus produces are many and vary with respect to their time of expression, their size, their sequence composition, and the cell type in which they are expressed. How the locus is regulated to function only in posterior compartment cells and how the locus functions to restrict the posterior compartment cells to grow only within the borders of the posterior compartments are two basic questions that remain intriguing but unanswered. We will approach these questions by 1) correlating specific phenotypes of different engrailed mutants with specific RNA transcripts from the locus; 2) defining the controlling sequence elements responsible for position and cell type specific expression of these RNA transcripts; and 3) identifying and characterizing the protein products of the locus.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
2R01GM030637-04
Application #
3278437
Study Section
Molecular Biology Study Section (MBY)
Project Start
1982-03-01
Project End
1988-03-31
Budget Start
1985-04-01
Budget End
1986-03-31
Support Year
4
Fiscal Year
1985
Total Cost
Indirect Cost
Name
University of California San Francisco
Department
Type
Schools of Medicine
DUNS #
073133571
City
San Francisco
State
CA
Country
United States
Zip Code
94143
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Kornberg, Thomas B (2017) Distributing signaling proteins in space and time: the province of cytonemes. Curr Opin Genet Dev 45:22-27
Kashima, Risa; Redmond, Patrick L; Ghatpande, Prajakta et al. (2017) Hyperactive locomotion in a Drosophila model is a functional readout for the synaptic abnormalities underlying fragile X syndrome. Sci Signal 10:
Kashima, Risa; Roy, Sougata; Ascano, Manuel et al. (2016) Augmented noncanonical BMP type II receptor signaling mediates the synaptic abnormality of fragile X syndrome. Sci Signal 9:ra58
Huang, Hai; Kornberg, Thomas B (2016) Cells must express components of the planar cell polarity system and extracellular matrix to support cytonemes. Elife 5:
Roy, Sougata; Kornberg, Thomas B (2015) Paracrine signaling mediated at cell-cell contacts. Bioessays 37:25-33
Yu, Dan; Baird, Michelle A; Allen, John R et al. (2015) A naturally monomeric infrared fluorescent protein for protein labeling in vivo. Nat Methods 12:763-5
Rao, Prashanth R; Lin, Li; Huang, Hai et al. (2015) Developmental compartments in the larval trachea of Drosophila. Elife 4:
Huang, Hai; Kornberg, Thomas B (2015) Myoblast cytonemes mediate Wg signaling from the wing imaginal disc and Delta-Notch signaling to the air sac primordium. Elife 4:e06114
Yu, Dan; Gustafson, William Clay; Han, Chun et al. (2014) An improved monomeric infrared fluorescent protein for neuronal and tumour brain imaging. Nat Commun 5:3626

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