The mechanisms controlling neural crest migration during craniofacial development are not well understood. The Eph/Ephrin cell signaling receptor-ligand pair has been identified as playing crucial roles during development, including controlling neural crest cell (NCC) migration. The ephrin-B ligands are also capable of transducing reverse signaling by virtue of their cytoplasmic C-terminal PDZ binding domain. In the case of ephrin-B1, this reverse signaling via the PDZ-binding domain is crucial for the proper migration of neural crest cells and normal craniofacial development. There are two specific aims for this application. First, I propose to identify and characterize mediators of ephrin-B1 reverse signaling during craniofacial development using an immunoprecipitation approach in NCCs. Second, I propose to identify and functionally characterize transcriptional targets of ephrin-B1 reverse signaling by inducing reverse signaling using a soluble EphB2-Fc fusion receptor in primary NCC culture and comparing expression profiles. The goal of this application is to understand molecular mechanisms of ephrin-B1 reverse signaling during craniofacial development. ? ? ?
| Bush, Jeffrey O; Soriano, Philippe (2010) Ephrin-B1 forward signaling regulates craniofacial morphogenesis by controlling cell proliferation across Eph-ephrin boundaries. Genes Dev 24:2068-80 |
| Bush, Jeffrey O; Soriano, Philippe (2009) Ephrin-B1 regulates axon guidance by reverse signaling through a PDZ-dependent mechanism. Genes Dev 23:1586-99 |
| Davy, Alice; Bush, Jeffrey O; Soriano, Philippe (2006) Inhibition of gap junction communication at ectopic Eph/ephrin boundaries underlies craniofrontonasal syndrome. PLoS Biol 4:e315 |
