Hallonet M, Hollemann T, Wehr R, Jenkins N A, Copeland N G, Pieler T, Gruss P
Max Planck Institut for Biophysical Chemistry, Department of Molecular and Cell Biology, Am Fassberg 11, Germany.
Development. 1998 Jul;125(14):2599-610. doi: 10.1242/dev.125.14.2599.
The vertebrate forebrain is formed at the rostral end of the neural plate under the regulation of local and specific signals emanating from both the endomesoderm and neuroectoderm. The development of the rostral and ventral forebrain in particular was difficult to study, mainly because no specific markers are available to date. Here, we report the identification of Vax1, a novel homeobox-containing gene identified in mouse, Xenopus and human. It is closely related to members of the Not and Emx gene families, all of which are required for the formation of structures where they are expressed. In mouse and Xenopus, Vax1 expression first occurs in the rostral neural plate, in the medial anterior neural ridge and adjacent ectoderm. Later, at midgestation in the mouse and tadpole stage in Xenopus, the expression remains confined in the derivatives of this territory which differentiate into rostromedial olfactory placode, optic nerve and disc, and anterior ventral forebrain. Together, these observations suggest that Vax1 could have an early evolutionary origin and could participate in the specification and formation of the rostral and ventral forebrain in vertebrates. Comparison of the limits of the expression territory of Vax1 with that of Dlx1, Pax6 and Emx1 indicates that the corticostriatal ridge is a complex structure with distinct identifiable genetic compartments. Besides, the study of Vax1 expression in Pax6-deficient homozygous brains indicates that its regulation is independent of Pax6, although the expression patterns of these two genes appear complementary in wild-type animals. Vax1 chromosomal location is mapped at the distal end of the mouse chromosome 19, linked with that of Emx2. These two genes may have arisen by tandem duplication. The Vax1 gene is thus an interesting new tool to study the rostral ventral forebrain patterning, morphogenesis and evolution as well as the terminal differentiation of the forebrain in mouse and Xenopus.
脊椎动物的前脑是在神经板的头端形成的,受来自内胚层和神经外胚层的局部和特定信号调控。尤其是头端和腹侧前脑的发育很难研究,主要是因为迄今为止尚无特异性标志物。在此,我们报告了Vax1的鉴定,这是一个在小鼠、非洲爪蟾和人类中鉴定出的含新同源异型框的基因。它与Not和Emx基因家族的成员密切相关,这些基因家族的所有成员对于它们所表达结构的形成都是必需的。在小鼠和非洲爪蟾中,Vax1首先在头端神经板、内侧前神经嵴和相邻外胚层中表达。后来,在小鼠的妊娠中期和非洲爪蟾的蝌蚪期,表达仍局限于该区域的衍生物中,这些衍生物分化为头内侧嗅基板、视神经和视盘以及前腹侧前脑。这些观察结果共同表明,Vax1可能有早期的进化起源,并可能参与脊椎动物头端和腹侧前脑的特化和形成。Vax1表达区域的界限与Dlx1、Pax6和Emx1的表达区域界限的比较表明,皮质纹状体嵴是一个具有不同可识别遗传区室的复杂结构。此外,对Pax6缺陷纯合子脑中Vax1表达的研究表明,其调控独立于Pax6,尽管这两个基因在野生型动物中的表达模式似乎是互补的。Vax1的染色体定位在小鼠19号染色体的远端,与Emx2的位置相连。这两个基因可能是通过串联重复产生的。因此,Vax1基因是研究小鼠和非洲爪蟾头端腹侧前脑模式形成、形态发生和进化以及前脑终末分化的一个有趣的新工具。