Wilm Thomas P, Solnica-Krezel Lilianna
Vanderbilt University, Department of Biological Sciences, VU Station B 351634, Nashville, TN 37235-1634, USA.
Development. 2005 Jan;132(2):393-404. doi: 10.1242/dev.01572.
During vertebrate development the dorsal gastrula or Spemann-Mangold organizer orchestrates axis formation largely by limiting the ventralizing and posteriorizing activity of bone morphogenetic proteins (BMPs). In mouse and Xenopus laevis, genes encoding the zinc finger transcriptional repressor Prdm1/Blimp1 (PR domain containing 1, with ZNF domain; previously named B lymphocyte-induced maturation protein 1) were recently shown to be expressed in the visceral endoderm and anterior endomesoderm, respectively, and the prechordal plate of gastrula stage embryos. Later in development Prdm1/Blimp1 is expressed in many other tissues, including pharyngeal arches, limb buds, otic vesicles, photoreceptor cell layer, slow muscle and cloaca. Based on misexpression and dominant-negative studies, Prdm1/Blimp1 was proposed to promote anterior endomesoderm and head development in Xenopus laevis. Here we report the isolation and functional characterization of zebrafish prdm1 exhibiting a dynamic and evolutionarily conserved expression pattern. Misexpression of prdm1 inhibits the formation of dorsoanterior structures and reduces expression of chordin, which encodes a BMP antagonist. Conversely, interference with Prdm1 translation using antisense morpholino oligonucleotides, increases chordin expression, while reducing expression of Bmp genes, and consequently dorsalizing the embryo. At the end of the gastrula period, prdm1 morphant embryos have enlarged animal-vegetal and anteroposterior embryonic axes. This altered embryo morphology is associated with augmented extension movements of dorsal tissues and normal posterior migration of ventral tissues. Additionally, Prdm1 activity is essential for proper development of slow muscle, the photoreceptor cell layer, branchial arches and pectoral fins. Our studies reveal essential roles for prdm1 in limiting the function of the gastrula organizer and regulating cell fate specification and morphogenetic processes in precise correspondence with its intricate expression pattern.
在脊椎动物发育过程中,背侧原肠胚或施佩曼-曼戈尔德组织者主要通过限制骨形态发生蛋白(BMPs)的腹侧化和后位化活性来协调轴的形成。在小鼠和非洲爪蟾中,最近发现编码锌指转录抑制因子Prdm1/Blimp1(含PR结构域和ZNF结构域;以前称为B淋巴细胞诱导成熟蛋白1)的基因分别在内脏内胚层和前端内胚层以及原肠胚期胚胎的脊索前板中表达。在发育后期,Prdm1/Blimp1在许多其他组织中表达,包括咽弓、肢芽、耳泡、感光细胞层、慢肌和泄殖腔。基于错误表达和显性负性研究,有人提出Prdm1/Blimp1在非洲爪蟾中促进前端内胚层和头部发育。在此,我们报告斑马鱼prdm1的分离及其功能特性,其呈现出动态且进化保守的表达模式。prdm1的错误表达会抑制背侧前部结构的形成,并降低编码BMP拮抗剂的脊索蛋白的表达。相反,使用反义吗啉代寡核苷酸干扰Prdm1的翻译会增加脊索蛋白的表达,同时降低Bmp基因的表达,从而使胚胎背侧化。在原肠胚期结束时,prdm1 morphant胚胎的动植物轴和前后胚胎轴增大。这种改变的胚胎形态与背侧组织扩展运动增强和腹侧组织正常向后迁移有关。此外,Prdm1活性对于慢肌、感光细胞层、鳃弓和胸鳍的正常发育至关重要。我们的研究揭示了prdm1在限制原肠胚组织者功能以及根据其复杂的表达模式精确调节细胞命运特化和形态发生过程中的重要作用。
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