(provided by Candidate): Signaling peptides provide essential instructive cues for early vertebrate development. A small number of signaling pathways has been thought to be sufficient to explain most if not all aspects of early development. This idea has been challenged by our recent discovery that ende encodes a novel, highly conserved secreted peptide with essential functions during embryogenesis. Genome-wide technologies have allowed us to identify several other short secreted peptides that are expressed during embryogenesis. The goal of the proposed research is to identify the functions of these novel signaling peptides, using zebrafish as a model system.
Aim 1 will investigate the roles of Ende in cell fate specification and cell migration during heart formation and identify its receptor.
Aim 2 will investigate the in vivo functions of an additional 5 uncharacterized, secreted peptides during development. These studies have already led to the discovery of Ende as a novel essential signaling molecule during embryogenesis and will identify the roles of additional signaling molecules in early development. The proposed research has the potential to uncover novel signaling pathways and identify molecules with possible applications in tissue repair and in vitro differentiation.

Public Health Relevance

Signaling molecules provide essential cues to guide animal development. This study will identify the developmental roles of novel signaling molecules and lay the foundation for tissue engineering and tissue repair.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Career Transition Award (K99)
Project #
5K99HD076935-02
Application #
8712230
Study Section
Pediatrics Subcommittee (CHHD)
Program Officer
Javois, Lorette Claire
Project Start
2013-08-06
Project End
2015-07-31
Budget Start
2014-08-01
Budget End
2015-07-31
Support Year
2
Fiscal Year
2014
Total Cost
$114,866
Indirect Cost
$8,486
Name
Harvard University
Department
Microbiology/Immun/Virology
Type
Schools of Arts and Sciences
DUNS #
082359691
City
Cambridge
State
MA
Country
United States
Zip Code
02138
Pauli, Andrea; Norris, Megan L; Valen, Eivind et al. (2014) Toddler: an embryonic signal that promotes cell movement via Apelin receptors. Science 343:1248636
Gagnon, James A; Valen, Eivind; Thyme, Summer B et al. (2014) Efficient mutagenesis by Cas9 protein-mediated oligonucleotide insertion and large-scale assessment of single-guide RNAs. PLoS One 9:e98186