Critical Role of the Matricellular Protein SPARC in Mediating Erythroid Progenitor Cell Development in Zebrafish

Abstract

Sparc (Osteonectin) is a multifunctional matricellular glycoprotein expressed by many differentiated cells. Members of this family mediate cell-matrix interactions rather than acting as structural components of the extracellular matrix and therefore can influence many remodelling events, including haematopoiesis. We have investigated the role of sparc in embryonic haematopoiesis, using a morpholino antisense oligonucleotidebased knockdown approach. Knockdown of sparc function resulted in specific erythroid progenitor cell differentiation defects that were highlighted by changes in gene expression and morphology, which could be rescued by injection of sparc mRNA. Furthermore, a comparison of blood phenotypes of sparc and fgfs knockdowns with similar defects and the sparc rescue of fgf21 blood phenotype places sparc downstream of fgf21 in the genetic network regulating haematopoiesis in zebrafish. These results establish a role for an extracellular matrix protein (Sparc) as an important regulator of embryonic haematopoiesis during early development in zebrafish.