Maeda R, Mood K, Jones T L, Aruga J, Buchberg A M, Daar I O
Regulation of Cell Growth Laboratory, National Cancer Institute-Frederick, Frederick, Maryland, MD 21702, USA.
Oncogene. 2001 Mar 15;20(11):1329-42. doi: 10.1038/sj.onc.1204250.
Meis1 (Myeloid Ecotropic viral Integration Site 1) is a homeobox gene that was originally isolated as a common site of viral integration in myeloid tumors of the BXH-2 recombinant inbred mice strain. We previously isolated a Xenopus homolog of Meis1 (Xmeis1). Here we show that Xmeis1 may play a significant role in neural crest development. In developing Xenopus embryos, Xmeis1 displays a broad expression pattern, but strong expression is observed in tissue of neural cell fate, such as midbrain, hindbrain, the dorsal portion of the neural tube, and neural crest derived branchial arches. In animal cap explants, overexpression of Xmeis1b, an alternatively spliced form of Xmeis1, induces expression of neural crest marker genes in the absence of mesoderm. Moreover, Xmeis1b induces XGli-3 and XZic3, pre-pattern genes involved at the earliest stages of neural crest development, and like these two genes, can induce ectopic pigmented cell masses when overexpressed in developing embryos. Misexpression of Xmeis1b also induces ectopic expression of neural crest markers along the antero-posterior axis of the neural tube in developing Xenopus embryos. In contrast, Xmeis1a, another splice variant, is much less effective at inducing these effects. These data suggest that Xmeis1b is involved in neural crest cell fate specification during embryogenesis, and can functionally intersect with the Gli/Zic signal transduction pathway.
Meis1（髓系嗜亲性病毒整合位点1）是一种同源异型盒基因，最初是作为BXH - 2重组近交小鼠品系髓系肿瘤中病毒整合的常见位点而分离出来的。我们之前分离出了Meis1的非洲爪蟾同源物（Xmeis1）。在此我们表明，Xmeis1可能在神经嵴发育中发挥重要作用。在发育中的非洲爪蟾胚胎中，Xmeis1呈现广泛的表达模式，但在神经细胞命运相关组织中观察到强表达，如中脑、后脑、神经管背侧部分以及神经嵴衍生的鳃弓。在动物帽外植体中，Xmeis1的一种可变剪接形式Xmeis1b的过表达在没有中胚层的情况下诱导神经嵴标记基因的表达。此外，Xmeis1b诱导XGli - 3和XZic3，这两个基因是参与神经嵴发育最早阶段的预模式基因，并且与这两个基因一样，在发育中的胚胎中过表达时可诱导异位色素细胞团的形成。Xmeis1b的错误表达还会在发育中的非洲爪蟾胚胎神经管的前后轴上诱导神经嵴标记物的异位表达。相比之下，另一种剪接变体Xmeis1a在诱导这些效应方面效果要差得多。这些数据表明，Xmeis1b在胚胎发生过程中参与神经嵴细胞命运的特化，并且在功能上可与Gli/Zic信号转导途径相交。
