Bibonne A, Néant I, Batut J, Leclerc C, Moreau M, Gilbert T
Université Toulouse 3, Centre de Biologie du Développement, Toulouse, France.
Biochim Biophys Acta. 2013 Jul;1833(7):1665-71. doi: 10.1016/j.bbamcr.2012.12.015. Epub 2012 Dec 31.
Numerous Ca(2+) signaling events have been associated with early development of vertebrate embryo, from fertilization to organogenesis. In Xenopus laevis, Ca(2+) signals are key regulators in the earliest steps of the nervous system development. If neural determination is one of the best-characterized examples of the role of Ca(2+) during embryogenesis, increasing literature supports a determining role of organogenesis and differentiation. In blastula the cells of the presumptive ectoderm (animal caps) are pluripotent and can be induced toward neural fate with an intracellular increase of free Ca(2+) triggered by caffeine. To identify genes that are transcribed early upon Ca(2+) stimuli and involved in neural determination, we have constructed a subtractive cDNA library between neuralized and non-neuralized animal caps. Here we present the expression pattern of three new Ca(2+)-sensitive genes: fus (fused in sarcoma), brd3 (bromodomain containing 3) and wdr5 (WD repeat domain 5) as they all represent potential regulators of the transcriptional machinery. Using in situ hybridization we illustrated the spatial expression pattern of fus, brd3 and wdr5 during early developmental stages of Xenopus embryos. Strikingly, their domains of expression are not restricted to neural territories. They all share a specific expression throughout renal organogenesis which has been found to rely also on Ca(2+) signaling. This therefore highlights the key function of Ca(2+) target genes in specific territories during early development. We propose that Ca(2+) signaling through modulation of fus, brd3 and wdr5 expressions can control the transcription machinery to achieve proper embryogenesis. This article is part of a Special Issue entitled: 12th European Symposium on Calcium.
从受精到器官发生,许多钙离子信号事件都与脊椎动物胚胎的早期发育有关。在非洲爪蟾中,钙离子信号是神经系统发育最早阶段的关键调节因子。如果神经决定是钙离子在胚胎发生过程中作用的最典型例子之一,那么越来越多的文献支持其在器官发生和分化中的决定性作用。在囊胚期,预定外胚层(动物帽)的细胞具有多能性,并且可以通过咖啡因触发的细胞内游离钙离子增加而被诱导向神经命运分化。为了鉴定在钙离子刺激后早期转录且参与神经决定的基因,我们构建了神经化和未神经化动物帽之间的消减cDNA文库。在此,我们展示了三个新的钙离子敏感基因的表达模式:fus(肉瘤融合基因)、brd3(含溴结构域3)和wdr5(WD重复结构域5),因为它们都代表转录机制的潜在调节因子。我们使用原位杂交技术说明了非洲爪蟾胚胎早期发育阶段fus、brd3和wdr5的空间表达模式。令人惊讶的是,它们的表达域并不局限于神经区域。它们在整个肾脏器官发生过程中都有特定的表达,而肾脏器官发生也依赖于钙离子信号。因此,这突出了钙离子靶基因在早期发育特定区域的关键功能。我们提出,通过调节fus、brd3和wdr5的表达,钙离子信号可以控制转录机制以实现正常的胚胎发生。本文是名为:第12届欧洲钙研讨会的特刊的一部分。