The initiation of diverse pathways of tissue differentiation along the dorsal-ventral (D-V) body axis of the early Drosophila embryo is controlled by a maternal morphogen called dorsal (dl). The long term goal of the proposed study is to determine how this morphogen gradient differentially regulates gene expression along the D-V axis. dl is a novel sequence-specific DNA binding protein that shares extensive homology with the mammalian rel and NF-kB regulatory factors. Peak levels of dl activate two target genes called twist and snail, which encode regulatory factors responsible for the differentiation of the ventral mesoderm. The two genes are expressed in overlapping, but noncoincident patterns due to their differential activation by the dl morphogen. A major goal of this study is to determine how small changes in the levels of the dl morphogen specify these distinct limits of gene expression. dl also influences cell fate by repressing gene expression, and is responsible for restricting the activities of the homeobox gene zerknullt (zen) to dorsal regions where it directs the differentiation of the amnioserosa. There are several dl binding sites in the zen promoter, and their activities will be evaluated using a combination of in vitro mutagenesis and P-transformation assays. Genetic studies will be done to determine whether regulatory factors responsible for the differentiation of the neuroectoderm are directly influenced by the dl morphogen. Finally, the proposed study will include the molecular characterization of a novel regulatory gene responsible for the differentiation of the dorsal epidermis, called screw.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM046638-03
Application #
3306078
Study Section
Cellular Biology and Physiology Subcommittee 1 (CBY)
Project Start
1991-07-01
Project End
1995-06-30
Budget Start
1993-07-01
Budget End
1994-06-30
Support Year
3
Fiscal Year
1993
Total Cost
Indirect Cost
Name
University of California San Diego
Department
Type
Schools of Arts and Sciences
DUNS #
077758407
City
La Jolla
State
CA
Country
United States
Zip Code
92093
Lim, Bomyi; Levine, Michael; Yamazaki, Yuji (2017) Transcriptional Pre-patterning of Drosophila Gastrulation. Curr Biol 27:286-290
Esposito, Emilia; Lim, Bomyi; Guessous, Ghita et al. (2016) Mitosis-associated repression in development. Genes Dev 30:1503-8
Fukaya, Takashi; Lim, Bomyi; Levine, Michael (2016) Enhancer Control of Transcriptional Bursting. Cell 166:358-368
Farley, Emma K; Olson, Katrina M; Zhang, Wei et al. (2015) Suboptimization of developmental enhancers. Science 350:325-8
Farley, Emma K; Olson, Katrina M; Levine, Michael S (2015) Regulatory Principles Governing Tissue Specificity of Developmental Enhancers. Cold Spring Harb Symp Quant Biol 80:27-32
Levine, Michael; Cattoglio, Claudia; Tjian, Robert (2014) Looping back to leap forward: transcription enters a new era. Cell 157:13-25
Levine, Michael (2014) The contraction of time and space in remote chromosomal interactions. Cell 158:243-244
Boettiger, Alistair Nicol; Levine, Michael (2013) Rapid transcription fosters coordinate snail expression in the Drosophila embryo. Cell Rep 3:8-15
Lagha, Mounia; Bothma, Jacques P; Esposito, Emilia et al. (2013) Paused Pol II coordinates tissue morphogenesis in the Drosophila embryo. Cell 153:976-87
Lagha, Mounia; Bothma, Jacques P; Levine, Michael (2012) Mechanisms of transcriptional precision in animal development. Trends Genet 28:409-16

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