Silver L, Palis J
University of Rochester Medical Center, Department of Pediatrics and Cancer Center, NY 14642, USA.
Blood. 1997 Feb 15;89(4):1154-64.
Hematopoiesis in the mouse conceptus begins in the visceral yolk (VYS), with primitive erythroblasts first evident in blood islands at the headfold stage (E8.0). VYS erythropoiesis is decreased or abrogated by targeted disruption of the hematopoietic transcription factors tal-1, rbtn2, GATA-1, and GATA-2. To better understand the potential roles of these genes, and to trace the initial temporal and spatial development of mammalian embryonic hematopoiesis, we examined their expression patterns, and that of betaH1-globin, in normal mouse conceptuses by means of in situ hybridization. Attention was focused on the 36-hour period from mid-primitive streak to early somite stages (E7.25 to E8.5), when the conceptus undergoes rapid morphologic changes with formation of the yolk sac and blood islands. Each of these genes was expressed in extraembryonic mesoderm, from which blood islands are derived. This VYS expression occurred in a defined temporal sequence: tal-1 and rbtn2 transcripts were detected earlier than the others, followed by GATA-2 and GATA-1, and then by betaH1-globin. Transcripts for all of these genes were present in VYS mesoderm cell masses at the neural plate stage (E7.5), indicating commitment of these cells to the erythroid lineage before the appearance of morphologically recognizable erythroblasts. By early somite stages (E8.5), GATA-2 mRNA expression is downregulated in VYS blood islands as terminal primitive erythroid differentiation proceeds. We conclude that primitive mammalian erythropoiesis arises during gastrulation through the ordered temporal expression of tal-1, rbtn2, GATA2, and GATA-1 in a subset of extraembryonic mesoderm cells. During the stages analyzed, tal-1 and rbtn2 expression was also present in posterior embryonic mesoderm, while GATA-1 and GATA-2 expression was evident in extraembryonic tissues of ectodermal origin.
小鼠胚胎的造血作用始于脏壁卵黄囊（VYS），原始成红细胞最早在头褶期（E8.0）的血岛中出现。通过靶向破坏造血转录因子tal-1、rbtn2、GATA-1和GATA-2，VYS的红细胞生成作用会减弱或消除。为了更好地理解这些基因的潜在作用，并追踪哺乳动物胚胎造血作用最初的时空发育过程，我们通过原位杂交技术检测了它们以及βH1-珠蛋白在正常小鼠胚胎中的表达模式。研究重点集中在从中期原条到早期体节阶段（E7.25至E8.5）的36小时时间段内，此时胚胎经历快速的形态变化，形成卵黄囊和血岛。这些基因中的每一个都在外胚层中胚层表达，血岛即来源于此。VYS中的这种表达按特定的时间顺序发生：tal-1和rbtn2转录本比其他转录本更早被检测到，随后是GATA-2和GATA-1，然后是βH1-珠蛋白。在神经板阶段（E7.5），所有这些基因的转录本都存在于VYS中胚层细胞团中，这表明在形态上可识别的成红细胞出现之前，这些细胞就已确定向红细胞谱系分化。到早期体节阶段（E8.5），随着终末原始红细胞分化的进行，VYS血岛中的GATA-2 mRNA表达下调。我们得出结论，原始哺乳动物红细胞生成作用在原肠胚形成期间，通过tal-1、rbtn2、GATA2和GATA-1在一部分外胚层中胚层细胞中的有序时间表达而产生。在分析的阶段中，tal-1和rbtn2的表达也存在于胚胎后中胚层，而GATA-1和GATA-2的表达在外胚层来源的胚外组织中明显可见。
