13-P006 Neural crest derived signals pattern the cranial sensory nervous system by repressing lens potential

Elucidating the gene regulatory networks that govern pharyngeal arch artery (PAA) development is an important goal, as such knowledge can help identify new genes implicated in the manifestation of cardiovascular disease. The transcription factor Tbx1 plays a vital role in PAA development and is a major contributor to cardiovascular disease associated with DiGeorge syndrome. In this report, we used various genetic approaches to reveal part of a signalling network by which Tbx1 controls PAA development. We investigated the critical role played by the homeobox-containing transcription factor Gbx2 downstream of Tbx1. We found that PAA formation requires the pharyngeal surface ectoderm (PSE) as a key signalling centre from where Gbx2, in response to Tbx1, triggers essential directional cues to adjacent cardiac neural crest cells (cNCCs) en route to caudal PAAs. Abrogation of this signal generates cNCC patterning defects leading to PAA abnormalities. Finally, we showed that the Slit/Robo signalling pathway is activated during cNCC migration and found that components of that pathway are affected in Gbx2 and Tbx1 mutant embryos at the time of PAA development. We propose that the spatio-temporal control of this tightly orchestrated network of genes participates in crucial aspects of PAA development.