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RESEARCH COMMUNICATION

Foxn4 directly regulates tbx2b expression and atrioventricular canal formation

¹ Department of Biochemistry and Biophysics, Programs in Developmental Biology, Genetics and Human Genetics, University of California, San Francisco, San Francisco, California 94158, USA; ² Department of Medicine, University of California, San Francisco, San Francisco, California 94158, USA; ³ Cardiovascular Research Institute, University of California, San Francisco, San Francisco, California 94158, USA; ⁴ Department of Physiology, Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, California 94158, USA

Cardiac chamber formation represents an essential evolutionary milestone that allows for the heart to receive (atrium) and pump (ventricle) blood throughout a closed circulatory system. Here, we reveal a novel transcriptional pathway between foxn4 and tbx genes that facilitates this evolutionary event. We show that the zebrafish gene slipjig, which encodes Foxn4, regulates the formation of the atrioventricular (AV) canal to divide the heart. sli/foxn4 is expressed in the AV canal, and its encoded product binds to a highly conserved tbx2 enhancer domain that contains Foxn4- and T-box-binding sites, both necessary to regulate tbx2b expression in the AV canal.

[Keywords: Atrioventricular canal; evolutionary development; Forkhead transcription factors; T-box transcription factors; calcium indicator; mutations]]

Received October 30, 2007; revised version accepted January 23, 2008.

⁶ E-MAIL Neil.Chi{at}ucsf.edu; FAX (415) 476-3892.

Supplemental material is available at http://www.genesdev.org.

Article is online at http://www.genesdev.org/cgi/doi/10.1101/gad.1629408.

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