The vertebrate body plan is patterned along its left-right axis during development. This ensures that organs are positioned asymmetrically within the body, and that individual organs such as the heart and lungs, adopt an asymmetric structure. Failure of this process during our embryonic development, results in life-threatening disorders such as congenital heart defects. Left-right patterning is governed largely by the asymmetric activity of the Nodal signaling pathway, used for intercellular communication, on the left side of the embryo. Here, we investigate the role of the protein Rab23 in embryonic Nodal signaling. Mouse embryos lacking Rab23 exhibit left-right patterning defects as a result of their failure to activate Nodal signaling on the left side. We will investigate whether Rab23 function is required within cells for their response to Nodal signals or for cells to produce functional signals that act on their neighbors. We will also use molecular methods in the embryo, as well as cells in culture, to test the hypothesis that Rab23 controls the secretion or modification of the signal GDF1, which acts together with Nodal to properly activate cellular responses.

Public Health Relevance

Defects in left-right patterning during human embryogenesis often lead to life-threatening conditions such as congenital heart defects. This proposal investigates the cellular and biochemical mechanisms that underlie left-right patterning in mammals.

Agency
National Institute of Health (NIH)
Type
Small Research Grants (R03)
Project #
5R03HD065092-02
Application #
8339877
Study Section
Developmental Biology Subcommittee (CHHD)
Program Officer
Mukhopadhyay, Mahua
Project Start
Project End
Budget Start
Budget End
Support Year
2
Fiscal Year
2012
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
08544
Fuller, Kimberly; O'Connell, Joyce T; Gordon, Julie et al. (2014) Rab23 regulates Nodal signaling in vertebrate left-right patterning independently of the Hedgehog pathway. Dev Biol 391:182-95