The developmental mutants of Drosophila melanogaster have been a rich and productive source for investigations into basic mechanisms of development. Indeed, the explosive progress in our understanding of the molecular events in early Drosophila embryogenesis already justified the extensive investments in basic genetic and developmental studies that have provided the requisite materials and conceptual foundation. This progress also justifies our optimism that the Drosophila system will continue to provide valuable insights. We have chosen to intensively study one such locus in Drosophila, engrailed. Studies of mutants indicate that the engrailed function is essential during the precellular stages of embryogenesis for the formation of the blastoderm, during the gastrulation period for normal segmentation, and throughout subsequent development for maintenance of the segmental and compartmental subdivisions. The gene has been cloned, the gene structure and transcription unit has been defined, and the engrailed protein has been isolated. This system is now poised for molecular and enzymological studies to establish how the gene is regulated to effects to precise a program of positional and temporal expression, and to determine how the engrailed protein performs its several roles. We will approach these goals by: (1) isolating cis and trans acting mutations that affect the regulation of the engrailed gene; (2) analyzing the cis regulatory elements of the engrailed promoter by DNA transformation, and by isolating and characterizing the enzymes that regulate transcription of the engrailed gene; and (3) studying the activities and behavior of the engrailed protein.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
2R01GM030637-07
Application #
3278438
Study Section
Molecular Biology Study Section (MBY)
Project Start
1982-03-01
Project End
1993-03-31
Budget Start
1988-04-01
Budget End
1989-03-31
Support Year
7
Fiscal Year
1988
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
Chen, Weitao; Huang, Hai; Hatori, Ryo et al. (2017) Essential basal cytonemes take up Hedgehog in the Drosophila wing imaginal disc. Development 144:3134-3144
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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