Department of Biochemistry, The Rappaport Family Institute for Research in the Medical Sciences, Faculty of Medicine, Technion, Israel Institute of Technology, Haifa 31096, Israel.
Dev Biol. 2010 Feb 1;338(1):50-62. doi: 10.1016/j.ydbio.2009.11.024. Epub 2009 Nov 24.
In Xenopus embryos, XMeis3 protein activity is required for normal hindbrain formation. Our results show that XMeis3 protein knock down also causes a loss of primary neuron and neural crest cell lineages, without altering expression of Zic, Sox or Pax3 genes. Knock down or inhibition of the Pax3, Zic1 or Zic5 protein activities extinguishes embryonic expression of the XMeis3 gene, as well as triggering the loss of hindbrain, neural crest and primary neuron cell fates. Ectopic XMeis3 expression can rescue the Zic knock down phenotype. HoxD1 is an XMeis3 direct-target gene, and ectopic HoxD1 expression rescues cell fate losses in either XMeis3 or Zic protein knock down embryos. FGF3 and FGF8 are direct target genes of XMeis3 protein and their expression is lost in XMeis3 morphant embryos. In the genetic cascade controlling embryonic neural cell specification, XMeis3 lies below general-neuralizing, but upstream of FGF and regional-specific genes. Thus, XMeis3 protein is positioned at a key regulatory point, simultaneously regulating multiple neural cell fates during early vertebrate nervous system development.
在非洲爪蟾胚胎中，XMeis3 蛋白的活性对于正常后脑形成是必需的。我们的结果表明，XMeis3 蛋白敲低也会导致初级神经元和神经嵴细胞谱系的丧失，而不会改变 Zic、Sox 或 Pax3 基因的表达。Pax3、Zic1 或 Zic5 蛋白活性的敲低或抑制会使 XMeis3 基因的胚胎表达失活，并触发后脑、神经嵴和初级神经元细胞命运的丧失。异位 XMeis3 表达可以挽救 Zic 敲低表型。HoxD1 是 XMeis3 的直接靶基因，异位 HoxD1 表达可以挽救 XMeis3 或 Zic 蛋白敲低胚胎中细胞命运的丧失。FGF3 和 FGF8 是 XMeis3 蛋白的直接靶基因，其在 XMeis3 形态发生胚胎中的表达丢失。在控制胚胎神经细胞特化的遗传级联中，XMeis3 位于一般神经化基因的下游，但位于 FGF 和区域特异性基因的上游。因此，XMeis3 蛋白位于关键调节点，在早期脊椎动物神经系统发育过程中同时调节多种神经细胞命运。
