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Published April 15, 2010 | Accepted Version
Journal Article Open

Pax2 and Pea3 synergize to activate a novel regulatory enhancer for spalt4 in the developing ear

Abstract

The transcription factor spalt4 is a key early-response gene in otic placode induction. Here, we characterize the cis-regulatory regions of spalt4 responsible for activation of its expression in the developing otic placode and report the isolation of a novel core enhancer. Identification and mutational analysis of putative transcription factor binding sites reveal that Pea3, a downstream effector of FGF signaling, and Pax2 directly activate spalt4 during ear development. Morpholino-mediated knock-down of each factor reduces or eliminates reporter expression. In contrast, combined over-expression of Pea3 and Pax2 drives ectopic reporter expression, suggesting that they function synergistically. These studies expand the gene regulatory network underlying early otic development by identifying direct inputs that mediate spalt4 expression.

Additional Information

© 2009 Elsevier Inc. Received 1 October 2009; revised 30 October 2009; accepted 2 November 2009. Available online 10 November 2009. This article was accepted in 2009 to celebrate the 50th anniversary of Developmental Biology. We thank Dr. Tatjana Sauka-Spengler for her expert help and advice through all aspects of this project. We would like to thank Dr. Hisato Kondoh for providing the pTK vectors. We also want to thank Dr. Tatiana Hochgreb for helping with the confocal microscope. This work was supported by USPHS grants DE16459 and HD037105.

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August 21, 2023
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