In order for embryonic development to proceed correctly and reproducibly, the expression of genes in individual cells of an embryo must be coordinated with precision. One way in which temporal and spatial coordination of gene expression is achieved is through the action of transcription factors, proteins which bind to DNA and regulate expression of specific target genes. In Drosophila embryos, the maternally provided transcription factor Bicoid (Bcd) provides the positional information to pattern the anterior-posterior (AP) axis of the embryo. Bcd protein diffuses from the anterior pole of the embryo and is known to bind to over 1000 sites in the genome, thereby activating at least twenty target genes at different positions along the AP axis. A traditional model suggests the positional information in an embryo is a direct readout of Bcd concentration. Although recent studies have challenged this model, the mechanistic relationship between local Bcd concentration, DNA binding, and target gene expression is unknown. The experiments proposed here aim to directly measure the in vivo concentration-dependence of Bcd DNA binding and target gene expression. This work will elucidate the effects of protein concentration on the ability of transcription factors to control the expression of their targets.

Public Health Relevance

In order for developing embryos to produce the correct cell types and tissues found in a multicellular organism, each cell in the early embryo must express different combinations of genes at different times throughout development. Proper gene expression is insured through the action of transcription factors, which bind to DNA and regulate the expression of genes. This project aims to study the transcription factor Bicoid in early Drosophila embryos, and to determine how Bicoid's DNA binding activity allows different genes to be expressed in different cells in the developing embryo.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Predoctoral Individual National Research Service Award (F31)
Project #
1F31HD082940-01
Application #
8833429
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Mukhopadhyay, Mahua
Project Start
2014-12-01
Project End
2017-11-30
Budget Start
2014-12-01
Budget End
2015-11-30
Support Year
1
Fiscal Year
2015
Total Cost
Indirect Cost
Name
Princeton University
Department
Biochemistry
Type
Schools of Arts and Sciences
DUNS #
002484665
City
Princeton
State
NJ
Country
United States
Zip Code
Hannon, Colleen E; Blythe, Shelby A; Wieschaus, Eric F (2017) Concentration dependent chromatin states induced by the bicoid morphogen gradient. Elife 6: