bif1 , a new BMP signaling inhibitor, regulates embryonic hematopoiesis in the zebrafish

• Published in: Development (Cambridge) Vol. 146; no. 6
• Main Authors: Ghersi, Joey J, Mahony, Christopher B, Bertrand, Julien Y
• Format: Journal Article
• Language: English
• Published: England 21.03.2019
• Subjects: Animals; Animals, Genetically Modified; Bone Morphogenetic Proteins - antagonists & inhibitors; Bone Morphogenetic Proteins - metabolism; Cell Lineage; Cell Nucleus - metabolism; Erythropoiesis - genetics; Gene Expression Regulation, Developmental; Green Fluorescent Proteins - metabolism; Hematopoiesis; Intracellular Signaling Peptides and Proteins - genetics; Intracellular Signaling Peptides and Proteins - physiology; Mice; Signal Transduction; Transcription Factors - metabolism; Zebrafish; Zebrafish Proteins - genetics; Zebrafish Proteins - physiology; Zinc Fingers; Erythropoiesis; BMP signaling; Zebrafish; Zinc finger proteins; Hematopoietic stem cells; Definitive hematopoiesis
• ISSN: 0950-1991; 1477-9129
• 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.