University of Geneva, School of Medicine, Department of Pathology and Immunology, CMU, University of Geneva, CH-1211 Geneva 4, Switzerland.
University of Geneva, School of Medicine, Department of Pathology and Immunology, CMU, University of Geneva, CH-1211 Geneva 4, Switzerland
Development. 2019 Mar 21;146(6):dev164103. doi: 10.1242/dev.164103.
Hematopoiesis maintains the entire blood system, and dysregulation of this process can lead to malignancies (leukemia), immunodeficiencies or red blood cell diseases (anemia, polycythemia vera). We took advantage of the zebrafish model that shares most of the genetic program involved in hematopoiesis with mammals to characterize a new gene of unknown function, , which is expressed in the erythroid lineage during primitive, definitive and adult hematopoiesis. This gene, required during primitive and definitive erythropoiesis, encodes a C2H2 zinc-finger protein that inhibits BMP signaling. We therefore named this gene blood-inducing factor 1 and BMP inhibitory factor 1 (). We identified a ortholog in , another fish, and in the mouse genome. Both genes also inhibit BMP signaling when overexpressed in zebrafish. In conclusion, we have deorphanized a new zebrafish gene of unknown function: codes for a zinc-finger protein that inhibits BMP signaling and also regulates primitive erythropoiesis and definitive hematopoiesis.
造血系统维持着整个血液系统，这个过程的失调可能导致恶性肿瘤（白血病）、免疫缺陷或红细胞疾病（贫血、真性红细胞增多症）。我们利用与哺乳动物在造血过程中具有大多数遗传程序共享的斑马鱼模型，来描述一个新的基因，其功能未知，在原始、定型和成人造血过程中在红细胞谱系中表达。这个基因在原始和定型红细胞生成过程中是必需的，它编码一个 C2H2 锌指蛋白，抑制 BMP 信号。因此，我们将这个基因命名为诱导血液因子 1 和 BMP 抑制因子 1（）。我们在另一种鱼类和小鼠基因组中鉴定到了一个 的同源基因。这两个基因在斑马鱼中过表达时也抑制 BMP 信号。总之，我们已经确定了一个新的功能未知的斑马鱼基因：编码一个锌指蛋白，抑制 BMP 信号，并调节原始红细胞生成和定型造血。
