The developmental compartments of Drosophila are areas in which growth and pattern are regulated. Each compartment is defined at its anterior margin by a parasegment border and at its posterior margin by a segment border. These borders establish limits to the growth of cells, and their integrity is essential to normal pattern formation. Our previous work has shown that these borders also define domains of expression for a number of genes, including the segment polarity genes engrailed, cubitus interruptus-Dominant, and hedgehog, as well as several other genes that had not been previously identified. With the experiments described in this application, we will determine how these genes are regulated, and we will establish how these genes contribute to the creation, maintenance, or regulative functions of compartments. 1) Regulation and function of engrailed. Since the engrailed gene plays a preeminent role maintaining compartment borders and regulating other compartment-specific functions, we will continue our study of its regulation and function. We will use a genetic screen to identify functions required for normal engrailed expression, and we will further characterize GAGA, a novel transcription factor we found that has an important role in engrailed transcription. To learn how engrailed protein recognizes and acts on the promoters of the genes it regulates, we will continue our efforts to identify downstream target genes, to define the sequences recognized by engrailed protein, to study the biochemical properties of the engrailed protein, and to identify other proteins that might be required for its interactions with target promoters. 2) Regulation and function of other compartment-specific genes. These genes are of two types - those expressed by the body of cells comprising either the anterior or posterior compartments, and those expressed only by the cells comprising the compartment borders. To learn how these genes expressed specifically in either the anterior or posterior compartments are regulated, we will use genetic and molecular techniques to investigate the expression of cubitus interruptus-Dominant and hedgehog as well as the recently identified genes A1318 and 110. We will determine whether engrailed directly regulates the expression of these genes. Little is known about the cellular properties and molecular specializations at compartment borders. However, our recent work provides new tools to investigate the unique characteristics of compartment border cells, specifically our discovery of a class of genes which are expressed solely among the cells which comprise the compartment borders. Investigations of these genes with respect to their regulation, expression, mutant phenotypes, and biochemical functions will be pursued.

National Institute of Health (NIH)
National Institute of General Medical Sciences (NIGMS)
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Molecular Biology Study Section (MBY)
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University of California San Francisco
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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
Roy, Sougata; Huang, Hai; Liu, Songmei et al. (2014) Cytoneme-mediated contact-dependent transport of the Drosophila decapentaplegic signaling protein. Science 343:1244624

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