Liu Jeh-Ping
Department of Neuroscience, University of Virginia, 409 Lane Road, MR4, Room 5032, Charlottesville, VA 22908, USA.
Development. 2006 Aug;133(15):2865-74. doi: 10.1242/dev.02478. Epub 2006 Jun 21.
Hoxc family transcription factors are expressed in different domains along the rostrocaudal (RC) axis of the developing spinal cord and they define RC identities of spinal neurons. Our previous study using an in vitro assay system demonstrated that Fgf and Gdf11 signals located around Hensen's node of chick embryos have the ability to induce profiled Hoxc protein expression. To investigate the function of Gdf11 in RC patterning of the spinal cord in vivo, we expressed Gdf11 in chick embryonic spinal cord by in ovo electroporation and found that ectopic expression of Gdf11 in the neural tissue causes a rostral displacement of Hoxc protein expression domains, accompanied by rostral shifts in the positions of motoneuron columns and pools. Moreover, ectopic expression of follistatin (Fst), an antagonist of Gdf11, has a converse effect and causes caudal displacement of Hox protein expression domains, as well as motoneuron columns and pools. Mouse mutants lacking Gdf11 function exhibit a similar caudal displacement of Hox expression domains, but the severity of phenotype increases towards the caudal end of the spinal cord, indicating that the function of Gdf11 is more important in the caudal spinal cord. We also provide evidence that Gdf11 induces Smad2 phosphorylation and activated Smad2 is able to induce caudal Hox gene expression. These results demonstrate that Gdf11 has an important function in determining Hox gene expression domains and RC identity in the caudal spinal cord.
Hoxc家族转录因子沿发育中脊髓的头尾轴（RC）在不同区域表达，它们决定了脊髓神经元的RC身份。我们之前使用体外检测系统的研究表明，位于鸡胚亨氏结周围的Fgf和Gdf11信号有能力诱导Hoxc蛋白的特异性表达。为了研究Gdf11在体内脊髓RC模式形成中的功能，我们通过卵内电穿孔在鸡胚脊髓中表达Gdf11，发现神经组织中Gdf11的异位表达导致Hoxc蛋白表达域向头侧移位，同时运动神经元柱和运动神经元池的位置也向头侧移动。此外，Gdf11的拮抗剂卵泡抑素（Fst）的异位表达具有相反的作用，导致Hox蛋白表达域以及运动神经元柱和运动神经元池向尾侧移位。缺乏Gdf11功能的小鼠突变体表现出类似的Hox表达域向尾侧移位，但表型的严重程度向脊髓尾端增加，这表明Gdf11的功能在脊髓尾端更为重要。我们还提供证据表明，Gdf11诱导Smad2磷酸化，激活的Smad2能够诱导尾侧Hox基因表达。这些结果表明，Gdf11在确定脊髓尾端的Hox基因表达域和RC身份方面具有重要功能。
