Many cardiac abnormalities in humans can be attributed to defects in the heart during early embryogenesis. Genetic pathways that regulate cardiac development are conserved from insects to humans. The insect heart is a linear tube that is analogous to the linear tube that forms during early stages of vertebrate heart development. The simple structure of the insect heart and the availability of molecular and genetic tools make the heart of the fruit fly an attractive model system for the study of the early events of vertebrate cardiogenesis. Directed cell migration is responsible for bringing specified heart progenitor cells to form the linear heart tube at the midline of the embryo. Interactions of cell surface receptors with molecules in the extracellular matrix are considered to be instrumental for assembly of vascular tissues. However, little is known about what specific guidance cues are participating in this process. Slit is an extracellular matrix molecule that is common to both insects and humans. Slit and its receptor proteins Robo and Robo2 are expressed in the developing Drosophila heart. Severe defects in the assembly of the heart tube are observed in embryos missing the Slit or Robo proteins, indicating that these molecules play an important role in this process. The precise mechanism by which Slit affects heart tube assembly has yet to be determined and is the focus of the research presented in this proposal. ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Predoctoral Individual National Research Service Award (F31)
Project #
5F31GM075393-02
Application #
7116746
Study Section
Minority Programs Review Committee (MPRC)
Program Officer
Toliver, Adolphus
Project Start
2005-09-01
Project End
2008-08-31
Budget Start
2006-09-01
Budget End
2007-08-31
Support Year
2
Fiscal Year
2006
Total Cost
$30,702
Indirect Cost
Name
University of Medicine & Dentistry of NJ
Department
Pathology
Type
Schools of Medicine
DUNS #
617022384
City
Piscataway
State
NJ
Country
United States
Zip Code
08854
Santiago-Martinez, Edgardo; Soplop, Nadine H; Patel, Rajesh et al. (2008) Repulsion by Slit and Roundabout prevents Shotgun/E-cadherin-mediated cell adhesion during Drosophila heart tube lumen formation. J Cell Biol 182:241-8
Santiago-Martinez, Edgardo; Soplop, Nadine H; Kramer, Sunita G (2006) Lateral positioning at the dorsal midline: Slit and Roundabout receptors guide Drosophila heart cell migration. Proc Natl Acad Sci U S A 103:12441-6