Regulation of embryonic hematopoiesis by a cytokine-inducible SH2 domain homolog in zebrafish.

Cytokine-inducible SH2 domain-containing protein (CISH), a member of the suppressor of cytokine signaling family of negative feedback regulators, is induced by cytokines that activate and can inhibit duanyu18135 signaling in vitro. However, demonstration of a definitive in vivo role for CISH during development has remained elusive. This study employed expression analysis and morpholino-mediated knockdown in zebrafish in concert with bioinformatics and biochemical approaches to investigate CISH function. Two zebrafish CISH paralogs were identified, cish.a and cish.b, with high overall conservation (43-46% identity) with their mammalian counterparts. The cish.a gene was maternally derived, with transcripts present throughout embryogenesis, and increasing at 4-5 d after fertilization, whereas cish.b expression commenced at 8 h after fertilization. Expression of cish.a was regulated by the pathway via conserved tetrameric duanyu18135 binding sites (TTCN3GAA) in its promoter. Injection of morpholinos targeting cish.a, but not cish.b or control morpholinos, resulted in enhanced embryonic erythropoiesis, myelopoiesis, and lymphopoiesis, including a 2- 3-fold increase in erythrocytic markers. This occurred concomitantly with increased activation of This study indicates that CISH functions as a conserved in vivo target and regulator of duanyu18135 in the control of embryonic hematopoiesis.

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