A novel role for retinoids in patterning the avian forebrain during presomite stages
A novel role for retinoids in patterning the avian forebrain during presomite stages
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DOI：
10.1242/dev.00423
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发表时间：
2003-05-01
期刊：
影响因子：
4.6
通讯作者：
Studer, M
中科院分区：
文献类型：
--
作者：
Halilagic, A;Zile, MH;Studer, M
类维甲酸，特别是维甲酸（RA），已知可诱导神经组织后路病变。然而，类视黄醛信号的改变会显著影响前肢发育。先前的报道已经证明了类维生素a在颅面和前脑结构中的后期作用，但在前脑结构中的早期作用尚未得到很好的理解。我们发现，参与合成类维生素a的酶在鸟类的下胚层和直接参与头部形成的组织中表达，如前终胚层和脊索前中胚层。我们发现，在维生素a缺乏（VAD）的鹌鹑模型中，从发育的第一阶段就缺乏生物活性的RA，前内胚层标记物如Bmp2， Bmp7， Hex和Wnt拮抗剂crescent在早期原肠胚形成期间受到影响。此外，脊索前中胚层和前瞻性腹侧远脑区标记物向后扩展，轴向中胚层Shh表达减少，Bmp2和Bmp7在神经管腹侧中线异常表达。在早期阶段，VAD胚胎增加了腹侧神经外胚层和前肠内胚层的细胞死亡，但正常的颅神经嵴产生，而在后期，头部间充质和腹侧神经外胚层发生了广泛的细胞凋亡。因此，VAD胚胎最终具有单个且减少的端脑囊泡和异常图案的间脑。因此，我们认为类维甲酸在前脑发育过程中具有双重作用。在早期原肠胚形成过程中，RA作用于前内胚层细胞，调节脊索前中内胚层诱导信号向上覆神经外胚层的前后位置认同。随后，在神经孔闭合时，RA通过调节参与颅面形态发生的信号分子，对额鼻突和前脑间质的模式化是必需的。
Retinoids, and in particular retinoic acid (RA), are known to induce posterior fates in neural tissue. However, alterations in retinoid signalling dramatically affect anterior development. Previous reports have demonstrated a late role for retinoids in patterning craniofacial and forebrain structures, but an earlier role in anterior patterning is not well understood. We show that enzymes involved in synthesizing retinoids are expressed in the avian hypoblast and in tissues directly involved in head patterning, such as anterior definitive endoderm and prechordal mesendoderm. We found that in the vitamin A-deficient (VAD) quail model, which lacks biologically active RA from the first stages of development, anterior endodermal markers such as Bmp2, Bmp7, Hex and the Wnt antagonist crescent are affected during early gastrulation. Furthermore, prechordal mesendodermal and prospective ventral telencephalic markers are expanded posteriorly, Shh expression in the axial mesoderm is reduced, and Bmp2 and Bmp7 are abnormally expressed in the ventral midline of the neural tube. At early somite stages, VAD embryos have increased cell death in ventral neuroectoderm and foregut endoderm, but normal cranial neural crest production, whereas at later stages extensive apoptosis occurs in head mesenchyme and ventral neuroectoderm. As a result, VAD embryos end up with a single and reduced telencephalic vesicle and an abnormally patterned diencephalon. Therefore, we propose that retinoids have a dual role in patterning the anterior forebrain during development. During early gastrulation, RA acts in anterior endodermal cells to modulate the anteroposterior (AP) positional identity of prechordal mesendodermal inductive signals to the overlying neuroectoderm. Later on, at neural pore closure, RA is required for patterning of the mesenchyme of the frontonasal process and the forebrain by modulating signalling molecules involved in craniofacial morphogenesis.