Abstract

The suppressor of cytokine signaling (SOCS) proteins play important roles in cytokine and growth factor signaling, where they act principally as negative feedback regulators, particularly of the downstream signal transducer and activator of transcription (STAT) transcription factors. This critical mode of regulation impacts on both development and homeostasis. However, understanding of the function of SOCS4 remains limited. To address this, we investigated one of the zebrafish SOCS4 paralogues, socs4a, analyzing its expression and the consequences of its ablation. The socs4a gene had a dynamic expression profile during zebrafish embryogenesis, with initial ubiquitous expression becoming restricted to sensory ganglion within the developing nervous system. The knockdown of zebrafish socs4a revealed novel roles in notochord development, as well as the formation of a functional sensory system.

Highlights

  • The suppressor of cytokine signaling (SOCS) family of proteins have been demonstrated to act as classical negative feedback regulators of cytokine and growth factor signaling

  • Transcripts of socs4a were evident at the 1-cell stage, indicating maternal derivation, but these declined slightly by 12 h post fertilization, before increasing again by 16 hpf, before decreasing from 31 hpf; steady expression remained to 6 days post fertilization

  • Zebrafish socs4a was found to be expressed throughout embryonic development, with the highest transcript levels identified from 16–48 hpf, a critical period in neuronal development [33]

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Summary

Introduction

The suppressor of cytokine signaling (SOCS) family of proteins have been demonstrated to act as classical negative feedback regulators of cytokine and growth factor signaling. Central to this is the induction of SOCS genes by downstream signal transducer and activator of transcription (STAT) proteins, the activity of which is impacted by SOCS proteins [1]. SOCS1–3, along with the differently named SOCS family member cytokine-inducible SH2-containing protein (CISH), function mainly in cytokine receptor signaling, and have been shown to play key roles in regulating blood and immune cell development and function [3]. Mice carrying a Socs gene mutation are fertile with no overt phenotype, they succumbed more rapidly to the influenza virus infection [6], while another report has suggested a role for SOCS4 in the regulation of primordial follicle activation in the ovary [9]

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