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CUL4A and CUL4B are closely related members in Cullin family and can each assemble a Cullin-RING E3 ligase complex (Cullin-RING Ligase 4A or 4B, CRL4A, or CRL4B) and participate in a variety of biological processes. Previously we showed that zebrafish  cul4a , but not  cul4b , is essential for cardiac and pectoral fin development. Here, we have identified  cul4a  as a crucial regulator of primitive erythropoiesis in zebrafish embryonic development. Depletion of  cul4a  resulted in a striking reduction of erythroid cells due to the inhibition of erythroid differentiation. Transcript levels for early hematopoietic regulatory genes including  scl ,  lmo2 , and  gata1  are significantly reduced in  cul4a -deficient embryos. Mechanistically, we demonstrated that  scl  and  gata1 , the central regulators of primitive hematopoiesis for erythroid determination, are transcriptionally upregulated by  cul4a . These findings demonstrate an important role for  cul4a  in primitive erythropoiesis and may bear implications in regeneration medicine of anemia and related diseases.

Cul4a promotes zebrafish primitive erythropoiesis via upregulating scl and gata1 expression