Distinct roles for Scl in erythroid specification and maturation in zebrafish

The stem cell leukemia (SCL) transcription factor is essential for vertebrate hematopoiesis. Using the powerful zebrafish model for embryonic analysis, we compared the effects of either reducint or ablating Scl using morpholino-modified antisense RNAs. Ablation of Scl resulted in loss of primitive and definitive hematopoiesis, consistent with its essential role in these processes. Interestingly, in embryos with severely reduced Scl levels, erythroid progenitors expressing gata1 and embryonic globin developed. Erythroid maturation was deficient in these Scl hypmorphs, supporting that Scl was required both for the erythroid specification and maturation steps, with maturation requiring higher Scl levels than specification. While all hematopoietic functions were rescued by wild-type Scl mRNA, an Scl DNA binding mutant rescued primitive and definitive hematopoiesis, but did not rescue primitive erythroid maturation. Together, we show that there is a distinct Scl hypomorphic phenotype and demonstrate that distinct functions are required for Scl's roles in the specification and differentiation of primitive and definitive hematopoietic lineages. Our results reveal that Scl participates in multiple processes requiring different levels and functions. Further we identify an Scl hypomorphic phenotype distinct from the null state.