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First published online August 21, 2009
doi: 10.1242/10.1242/dev.028902

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Tbx1 controls cardiac neural crest cell migration during arch artery development by regulating Gbx2 expression in the pharyngeal ectoderm

¹ Molecular Medicine Unit, Institute of Child Health, 30 Guilford Street, London WC1N 1EH, UK.
² Department of Cell and Developmental Biology, University College London, London WC1E 6BT, UK.
³ Institute of Biosciences and Technology, Texas A&M Health Science Center, Houston, TX 77030, USA.
⁴ Departments of Pediatrics, Neurobiology and Anatomy and Human Genetics, University of Utah, Salt Lake City, UT 84112, USA.
⁵ Dulbecco Telethon Institute, c/o Telethon Institute of Genetics and Medicine, Via Pietro Castellino 111, 80131 Napoli, Italy.
⁶ Department of Craniofacial Development, King's College London, Floor 27, Guy's Tower, London SE1 9RT, UK.

^* Author for correspondence (p.scambler{at}ich.ucl.ac.uk)

Accepted 16 July 2009

Elucidating the gene regulatory networks that govern pharyngeal arch artery (PAA) development is an important goal, as such knowledge can help to identify new genes involved in 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 in mice. We investigated the crucial role played by the homeobox-containing transcription factor Gbx2 downstream of Tbx1. We found that PAA formation requires the pharyngeal surface ectoderm as a key signalling centre from which Gbx2, in response to Tbx1, triggers essential directional cues to the adjacent cardiac neural crest cells (cNCCs) en route to the 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 that components of this pathway are affected in Gbx2 and Tbx1 mutant embryos at the time of PAA development. We propose that the spatiotemporal control of this tightly orchestrated network of genes participates in crucial aspects of PAA development.

Key words: Pharyngeal arch arteries, Cardiac neural crest, Slit/Robo, Mouse

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