Using the Zebrafish as a Genetic Model to Study Erythropoiesis

Abstract

Vertebrates generate mature red blood cells (RBCs) via a highly regulated, multistep process called erythropoiesis. Erythropoiesis involves synthesis of heme and hemoglobin, clearance of the nuclei and other organelles, and remodeling of the plasma membrane, and these processes are exquisitely coordinated by specific regulatory factors including transcriptional factors and signaling molecules. Defects in erythropoiesis can lead to blood disorders such as congenital dyserythropoietic anemias, Diamond–Blackfan anemias, sideroblastic anemias, myelodysplastic syndrome, and porphyria. The molecular mechanisms of erythropoiesis are highly conserved between fish and mammals, and the zebrafish (Danio rerio) has provided a powerful genetic model for studying erythropoiesis. Studies in zebrafish have yielded important insights into RBC development and established a number of models for human blood diseases. Here, we focus on latest discoveries of the molecular processes and mechanisms regulating zebrafish erythropoiesis and summarize newly established zebrafish models of human anemias.

Zebrafish ELL-associated factors Eaf1/2 modulate erythropoiesis via regulating gata1a expression and WNT signaling to facilitate hypoxia tolerance

“…In this study, we unveil a function of eaf1 and eaf2 in erythropoiesis and hypoxia tolerance in zebrafish. Our study provides new insights into the molecular mechanism underlying erythropoiesis, which not only has general implications in regeneration medicine of anemia and related diseases, but also provides evidence that genes eaf1 and eaf2 are important molecules in modulating fish economic or productive traits, such as growth, disease resistance, hypoxia tolerance, and so on (Gui et al 2021 ; Kafina and Paw 2018 ; Patton et al 2021 ; Zhang et al 2021 ).…”

“…Each step of erythropoiesis is exquisitely regulated by specific factors, especially transcription factors and signaling molecules (Zhang et al 2021 ). Scl ( tal1 ) and lmo2 are two primitive progenitor cell marker genes with pivotal functions in erythropoiesis (de Jong and Zon 2005 ).…”

“…Zebrafish ( Danio rerio ) is an ideal model for hematopoiesis research because its transparency greatly facilitates the visualization of blood cell formation (de Jong and Zon 2005 ; Paik and Zon 2010 ). Hematopoietic development in zebrafish has been considered to comprise two major overlapping hematopoiesis stages: “primitive” and “definitive” phases, both producing red blood cells (RBCs) (Davidson and Zon 2004 ; Paik and Zon 2010 ; Zhang et al 2021 ). A sophisticated network of lineage-specific transcription factors Scl/Tal1 , Gata1 , and Lmo2 was shown to function pivotally and essentially in erythrogenesis via regulating the expression of erythropoietic genes (Dooley et al 2005 ; Ferreira et al 2005 ; Galloway et al 2005 ; Patterson et al 2007 ).…”

Molecular regulatory mechanisms of erythropoiesis and related diseases

“…Mammals are distinguished by their highly condensed nuclei, which undergo extrusion and nuclei elimination during the final stage of erythropoiesis, the pre‐erythrocytic stage. In other organisms, such as fish, reptiles, amphibians, and birds, nucleus condensation occurs, but nucleus removal does not 10 …”

“…In other organisms, such as fish, reptiles, amphibians, and birds, nucleus condensation occurs, but nucleus removal does not. 10 In mammals and other vertebrates, terminal erythropoiesis is accompanied by an increase in hemoglobin and a decrease in nuclear activity. Late middle-aged erythrocytes have the highest concentration of hemoglobin, while the nucleus volume decreases by a factor of 10.…”