title: Suppressor of cytokine signaling 1 regulates embryonic myelopoiesis independently of its effects on T cell development.
abstract: Suppressor of cytokine signaling 1 (SOCS1) has been shown to play important roles in the immune system. It acts as a key negative regulator of signaling via receptors for IFNs and other cytokines controlling T cell development, as well as Toll receptor signaling in macrophages and other immune cells. To gain further insight into SOCS1, we have identified and characterized the zebrafish socs1 gene, which exhibited sequence and functional conservation with its mammalian counterparts. Initially maternally derived, the socs1 gene showed early zygotic expression in mesodermal structures, including the posterior intermediate cell mass, a site of primitive hematopoiesis. At later time points, expression was seen in a broad anterior domain, liver, notochord, and intersegmental vesicles. Morpholino-mediated knockdown of socs1 resulted in perturbation of specific hematopoietic populations prior to the commencement of lymphopoiesis, ruling out T cell involvement. However, socs1 knockdown also lead to a reduction in the size of the developing thymus later in embryogenesis. Zebrafish SOCS1 was shown to be able to interact with both zebrafish Jak2a and Stat5.1 in vitro and in vivo. These studies demonstrate a conserved role for SOCS1 in T cell development and suggest a novel T cell-independent function in embryonic myelopoiesis mediated, at least in part, via its effects on receptors using the Jak2-Stat5 pathway.
authors.affiliation: School of Life and Environmental Sciences, Deakin University, Burwood, Victoria 3125, Australia.
authors.forename: Lynda A
authors.initials: LA
authors.lastname: O'Sullivan
authors.forename: Suzita M
authors.initials: SM
authors.lastname: Noor
authors.forename: Monique C
authors.initials: MC
authors.lastname: Trengove
authors.forename: Rowena S
authors.initials: RS
authors.lastname: Lewis
authors.forename: Clifford
authors.initials: C
authors.lastname: Liongue
authors.forename: Naomi S
authors.initials: NS
authors.lastname: Sprigg
authors.forename: Sandra E
authors.initials: SE
authors.lastname: Nicholson
authors.forename: Alister C
authors.initials: AC
authors.lastname: Ward
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites / Q000235:genetics; D003001:Cloning, Molecular; D004625:Embryo, Nonmammalian / Q000098:blood supply / Q000196:embryology / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D055786:Gene Knockout Techniques; D057809:HEK293 Cells; D006801:Humans; D017403:In Situ Hybridization; D008969:Molecular Sequence Data; D038042:Myelopoiesis; D010802:Phylogeny; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050799:STAT5 Transcription Factor / Q000378:metabolism; D017422:Sequence Analysis, DNA; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000145:classification / Q000235:genetics* / Q000378:metabolism; D013601:T-Lymphocytes / Q000378:metabolism*; D015027:Zebrafish / Q000196:embryology / Q000235:genetics*; D029961:Zebrafish Proteins / Q000145:classification / Q000235:genetics* / Q000378:metabolism
chemical_list: D050799:STAT5 Transcription Factor; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D029961:Zebrafish Proteins; C494098:ihb394 protein, zebrafish; C540939:socs1a protein, zebrafish; D011505:Protein-Tyrosine Kinases; C534485:Jak2a protein, zebrafish