Peng Gang, Westerfield Monte
Institute of Neuroscience, University of Oregon, Eugene, OR 97403-1254, USA.
Development. 2006 Aug;133(16):3191-200. doi: 10.1242/dev.02485. Epub 2006 Jul 19.
In vertebrate embryos, induction and patterning of the forebrain require the local inhibition of caudalizing signals, such as Wnts, emanating from the mesendoderm and caudal brain. Here, we report that Lhx5, expressed in the rostral neuroectoderm, regulates the local inhibition of Wnts. Activation of Lhx5 expands forebrain structures, whereas inhibition of Lhx5 function compromises forebrain development in zebrafish embryos. Lhx5 can rescue forebrain deficiencies caused by excess Wnt activity, and inhibition of Lhx5 function results in ectopic activation of Wnt signaling. Lhx5 regulates the expression of two secreted Frizzled-related Wnt antagonists, Sfrp1a and Sfrp5. These Sfrps can reduce the ectopic activation of Wnt signaling and rescue the forebrain deficiencies caused by inhibition of Lhx5 function. Our results demonstrate that Lhx5 is a required factor that promotes forebrain development and inhibits Wnt signaling by activating the transcription of secreted Wnt antagonists.
在脊椎动物胚胎中，前脑的诱导和模式形成需要局部抑制来自中内胚层和后脑发出的尾部化信号，如Wnt信号。在此，我们报道在头侧神经外胚层表达的Lhx5调节对Wnt信号的局部抑制。Lhx5的激活会扩大前脑结构，而抑制Lhx5的功能则会损害斑马鱼胚胎的前脑发育。Lhx5可以挽救由过量Wnt活性引起的前脑缺陷，抑制Lhx5的功能会导致Wnt信号的异位激活。Lhx5调节两种分泌型卷曲相关Wnt拮抗剂Sfrp1a和Sfrp5的表达。这些Sfrp可以减少Wnt信号的异位激活，并挽救由抑制Lhx5功能引起的前脑缺陷。我们的结果表明，Lhx5是促进前脑发育并通过激活分泌型Wnt拮抗剂的转录来抑制Wnt信号的必需因子。
