Sugimoto Kaoru, Okabayashi Koji, Sedohara Ayako, Hayata Tadayoshi, Asashima Makoto
Department of Life Sciences, Graduate School of Arts and Sciences, The University of Tokyo, Tokyo, Japan.
Dev Neurosci. 2007;29(6):468-79. doi: 10.1159/000097320. Epub 2006 Nov 20.
In early neural development, active cell proliferation and apoptosis take place concurrent with cell differentiation, but how these processes are coordinated remains unclear. In this study, we characterized the role of XBtg2 in Xenopus neural development. XBtg2 transcripts were detected at the edge of the anterolateral neural plate and the neural crest region at the midneurula stage, and in eyes and in part of the neural tube at the tailbud stage. Translational inhibition of XBtg2 affected anterior neural development and impaired eye formation. XBtg2 depletion altered the expression patterns of the early neural genes, Zic3 and SoxD, at the midneurula stage, but not at the early neurula stage. At the midneurula stage, XBtg2-depleted embryos exhibited a marked decrease in the expression of anterior neural genes, En2, Otx2, and Rx1, without any changes in neural crest genes, Slug and Snail, or an epidermal gene, XK81. These results suggest that XBtg2 is required for the differentiation of the anterior neural plate from the midneurula stage, but not for the specification of the fate and patterning of the neural plate. XBtg2-depleted embryos also exhibited an increase in both proliferation and apoptosis in the anterior neural plate; however, the altered expression patterns of neural markers were not reversed by inhibition of either the cell cycle or apoptosis. Based on these data, we propose that XBtg2 plays an essential role in the anterior neural development, by regulating neural cell differentiation, and, independently, cell proliferation and survival.
在神经发育早期,活跃的细胞增殖和凋亡与细胞分化同时发生,但这些过程如何协调仍不清楚。在本研究中,我们确定了XBtg2在非洲爪蟾神经发育中的作用。在神经胚中期,在神经板前外侧边缘和神经嵴区域检测到XBtg2转录本,在尾芽期,在眼睛和部分神经管中检测到该转录本。对XBtg2的翻译抑制影响前脑发育并损害眼睛形成。XBtg2缺失改变了神经胚中期早期神经基因Zic3和SoxD的表达模式,但在神经胚早期未改变。在神经胚中期,XBtg2缺失的胚胎前脑神经基因En2、Otx2和Rx1的表达明显下降,而神经嵴基因Slug和Snail或表皮基因XK81没有任何变化。这些结果表明,从神经胚中期开始,XBtg2是前神经板分化所必需的,但不是神经板命运决定和模式形成所必需的。XBtg2缺失的胚胎在前神经板中的增殖和凋亡也增加;然而,抑制细胞周期或凋亡并不能逆转神经标记物表达模式的改变。基于这些数据,我们认为XBtg2通过调节神经细胞分化以及独立地调节细胞增殖和存活,在前脑发育中发挥重要作用。