(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.
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.
|Chew, Guo-Liang; Pauli, Andrea; Schier, Alexander F (2016) Conservation of uORF repressiveness and sequence features in mouse, human and zebrafish. Nat Commun 7:11663|
|Pauli, Andrea; Montague, Tessa G; Lennox, Kim A et al. (2015) Antisense Oligonucleotide-Mediated Transcript Knockdown in Zebrafish. PLoS One 10:e0139504|
|Pauli, Andrea; Valen, Eivind; Schier, Alexander F (2015) Identifying (non-)coding RNAs and small peptides: challenges and opportunities. Bioessays 37:103-12|
|Rabani, Michal; Raychowdhury, Raktima; Jovanovic, Marko et al. (2014) High-resolution sequencing and modeling identifies distinct dynamic RNA regulatory strategies. Cell 159:1698-710|
|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|
|Pauli, Andrea; Norris, Megan L; Valen, Eivind et al. (2014) Toddler: an embryonic signal that promotes cell movement via Apelin receptors. Science 343:1248636|