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Long-range action of Nodal requires interaction with GDF1

¹ Developmental Genetics Group, Graduate School of Frontier Biosciences, Osaka University, and CREST, Japan Science and Technology Corporation (JST), Suita, Osaka 565-0871, Japan; ² Department of Neurobiology and Anatomy, and The Eccles Program in Human Molecular Biology and Genetics, University of Utah, Salt Lake City, Utah 84112, USA

GDF1 (growth/differentiation factor 1), a Vg1-related member of the transforming growth factor-β superfamily, is required for left–right patterning in the mouse, but the precise function of GDF1 has remained largely unknown. In contrast to previous observations, we now show that GDF1 itself is not an effective ligand but rather functions as a coligand for Nodal. GDF1 directly interacts with Nodal and thereby greatly increases its specific activity. Gdf1 expression in the node was found necessary and sufficient for initiation of asymmetric Nodal expression in the lateral plate of mouse embryos. Coexpression of GDF1 with Nodal in frog embryos increased the range of the Nodal signal. Introduction of Nodal alone into the lateral plate of Gdf1 knockout mouse embryos did not induce Lefty1 expression at the midline, whereas introduction of both Nodal and GDF1 did, showing that GDF1 is required for long-range Nodal signaling from the lateral plate to the midline. These results suggest that GDF1 regulates the activity and signaling range of Nodal through direct interaction.

[Keywords: Embryonic patterning; GDF1; left–right axis; Nodal; signaling]]

Received May 31, 2007; revised version accepted October 29, 2007.

⁴ Corresponding author.

E-MAIL hamada{at}fbs.osaka-u.ac.jp; FAX 81-6-6878-9846.

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

Article is online at http://www.genesdev.org/cgi/doi/10.1101/gad.1623907

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