Tanaka Chinatsu, Sakuma Rui, Nakamura Tetsuya, Hamada Hiroshi, Saijoh Yukio
Developmental Genetics Group, Graduate School of Frontier Biosciences, Osaka University, and CREST, Japan Science and Technology Corporation (JST), Suita, Osaka 565-0871, Japan.
Genes Dev. 2007 Dec 15;21(24):3272-82. doi: 10.1101/gad.1623907.
GDF1 (growth/differentiation factor 1), a Vg1-related member of the transforming growth factor-beta 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.
生长分化因子1（GDF1）是转化生长因子-β超家族中与Vg1相关的成员，在小鼠左右模式形成中是必需的，但GDF1的确切功能在很大程度上仍不清楚。与之前的观察结果相反，我们现在表明GDF1本身不是一种有效的配体，而是作为Nodal的共配体发挥作用。GDF1直接与Nodal相互作用，从而大大增加其比活性。发现在小鼠胚胎侧板中启动不对称Nodal表达，节点中的Gdf1表达是必要且充分的。在青蛙胚胎中GDF1与Nodal共表达增加了Nodal信号的范围。单独将Nodal引入Gdf1基因敲除小鼠胚胎的侧板中不会在中线诱导Lefty1表达，而同时引入Nodal和GDF1则会诱导，这表明GDF1是从侧板到中线的长距离Nodal信号传导所必需的。这些结果表明GDF1通过直接相互作用调节Nodal的活性和信号范围。
