Syndecan 2 regulates hematopoietic lineages and infection resolution in zebrafish

Syndecan 2 () is a transmembrane cell-surface heparan sulfate proteoglycan (HSPG) that has been implicated in the regulation of cell-cell signaling pathways and cell-matrix interactions. Surprisingly, homozygous recessive maternal zygotic (MZ) null mutants in zebrafish appear to have normal development, normal morphology and are viable and fertile in adulthood. Whole transcriptome RNA sequencing, FACS analyses, and imaging of transgenic reporter lines that distinguish specific hematopoietic lineages revealed that mutants have defects in the specification and proportions of red blood cells and neutrophils that initiate during embryonic hematopoiesis and likely persist through adulthood. During bacterial infections, MZ mutants have markedly reduced neutrophil recruitment and significantly higher death rates. Hematopoietic stem/progenitor cell (HSPC) numbers are also significantly reduced in MZ mutants. In zebrafish, cells that bud off of the ventral region of somites are thought to give rise to the reticular stromal cells of the caudal hematopoietic tissue (CHT) stem cell niche. In MZ mutants, these budding cells have abberant blebbing morphology associated with widespread apoptosis during induction of HSPCs and with changes in the vascularization and stromal cell structure of the CHT stem cell niche. This suggests that loss of disrupts the earliest events of definitive hematopoiesis. Our findings of hematopoietic defects, nascent immune system alterations and inability to resolve infection in mutants sets the stage for examining the roles of HSPG genes in a wide range of hematopoietic and immune defects in humans.