The development of multicellular animals requires the coordinated activities of cell-cell signaling pathways and cell-type specific transcription factors. In this project, how these inputs are orchestrated during the development of animal appendages will be investigated. Using Drosophila melanogaster as the model system, the focus is how two signaling pathways, Wingless (Wg) and the BMP homolog Decapentaplegic (Dpp), create the proximo-distal (PD) axis of the leg. Previous work established that Wg and Dpp combine to activate the transcription of target genes at discreet positions along the PD axis. However, how these signals translate to transcriptional activation is not understood. Using reporter gene and DNA binding analyses, how PD genes are activated along the PD axis will be investigated. Second, a novel method to analyze the chromatin structure of PD gene regulatory sequences will be employed. Third, the role that cellular proliferation dynamics play in PD gene regulation will be investigated. These studies will impact public health in several ways. First, the mechanism by which secreted signals activate gene expression is common to many aspects of animal development and disease. Thus, a better understanding of these basic mechanisms is critical for deciphering how these pathways, when altered, contribute to diseases such as cancer. Second, many human birth defects are due to problems in the development of the appendages. As many of the transcription factors, signaling molecules, and underlying mechanisms controlling appendage development are conserved between Drosophila and humans, it is likely that a more comprehensive dissection of these processes in an experimentally powerful system such as Drosophila will provide important insights into these human birth defects.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
3R01GM058575-09A1S1
Application #
7480171
Study Section
Development - 1 Study Section (DEV1)
Program Officer
Haynes, Susan R
Project Start
1999-01-01
Project End
2010-12-31
Budget Start
2007-07-01
Budget End
2007-12-31
Support Year
9
Fiscal Year
2007
Total Cost
$18,000
Indirect Cost
Name
Columbia University (N.Y.)
Department
Biochemistry
Type
Schools of Medicine
DUNS #
621889815
City
New York
State
NY
Country
United States
Zip Code
10032
Newcomb, Susan; Voutev, Roumen; Jory, Aurelie et al. (2018) cis-regulatory architecture of a short-range EGFR organizing center in the Drosophila melanogaster leg. PLoS Genet 14:e1007568
Requena, David; Álvarez, Jose Andres; Gabilondo, Hugo et al. (2017) Origins and Specification of the Drosophila Wing. Curr Biol 27:3826-3836.e5
Voutev, Roumen; Mann, Richard S (2017) Bxb1 phage recombinase assists genome engineering in Drosophila melanogaster. Biotechniques 62:37-38
Voutev, Roumen; Mann, Richard S (2016) Streamlined scanning for enhancer elements in Drosophila melanogaster. Biotechniques 60:141-4
Zhou, Tianyin; Shen, Ning; Yang, Lin et al. (2015) Quantitative modeling of transcription factor binding specificities using DNA shape. Proc Natl Acad Sci U S A 112:4654-9
Riley, Todd R; Lazarovici, Allan; Mann, Richard S et al. (2015) Building accurate sequence-to-affinity models from high-throughput in vitro protein-DNA binding data using FeatureREDUCE. Elife 4:
Abe, Namiko; Dror, Iris; Yang, Lin et al. (2015) Deconvolving the recognition of DNA shape from sequence. Cell 161:307-18
Agelopoulos, Marios; McKay, Daniel J; Mann, Richard S (2014) cgChIP: a cell type- and gene-specific method for chromatin analysis. Methods Mol Biol 1196:291-306
Slattery, Matthew; Voutev, Roumen; Ma, Lijia et al. (2013) Divergent transcriptional regulatory logic at the intersection of tissue growth and developmental patterning. PLoS Genet 9:e1003753
Oh, Hyangyee; Slattery, Matthew; Ma, Lijia et al. (2013) Genome-wide association of Yorkie with chromatin and chromatin-remodeling complexes. Cell Rep 3:309-18

Showing the most recent 10 out of 25 publications