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First published online 5 October 2005
doi: 10.1242/dev.02059

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Tead proteins activate the Foxa2 enhancer in the node in cooperation with a second factor

Atsushi Sawada¹, Yuriko Nishizaki^2,*, Hiroko Sato¹, Yukari Yada¹, Rika Nakayama³, Shinji Yamamoto¹, Noriyuki Nishioka¹, Hisato Kondoh² and Hiroshi Sasaki^1,

¹ Laboratory for Embryonic Induction, RIKEN Center for Developmental Biology, 2-2-3 Minatojima-minamimachi, Chuo-ku, Kobe, Hyogo 650-0047, Japan
² Graduate School of Frontier Biosciences, Osaka University, 1-3 Yamadaoka, Suita, Osaka 565-0871, Japan
³ Laboratory for Animal Resources and Genetic Engineering (LARGE), RIKEN Center for Developmental Biology, 2-2-3 Minatojima-minamimachi, Chuo-ku, Kobe, Hyogo 650-0047, Japan

Author for correspondence (e-mail: sasaki{at}cdb.riken.jp)

Accepted 24 August 2005

The cell population and the activity of the organizer change during the course of development. We addressed the mechanism of mouse node development via an analysis of the node/notochord enhancer (NE) of Foxa2. We first identified the core element (CE) of the enhancer, which in multimeric form drives gene expression in the node. The CE was activated in Wnt/ß-catenin-treated P19 cells with a time lag, and this activation was dependent on two separate sequence motifs within the CE. These same motifs were also required for enhancer activity in transgenic embryos. We identified the Tead family of transcription factors as binding proteins for the 3' motif. Teads and their co-factor YAP65 activated the CE in P19 cells, and binding of Tead to CE was essential for enhancer activity. Inhibition of Tead activity by repressor-modified Tead compromised NE enhancer activation and notochord development in transgenic mouse embryos. Furthermore, manipulation of Tead activity in zebrafish embryos led to altered expression of foxa2 in the embryonic shield. These results suggest that Tead activates the Foxa2 enhancer core element in the mouse node in cooperation with a second factor that binds to the 5' element, and that a similar mechanism also operates in the zebrafish shield.

Key words: Tead, Node, Foxa2, Notochord, Enhancer, Mouse

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