SOCS3 is required to temporally fine-tune photoreceptor cell differentiation
SOCS3 is required to temporally fine-tune photoreceptor cell differentiation
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DOI：
10.1016/j.ydbio.2006.11.032
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发表时间：
2007-03-15
影响因子：
2.7
通讯作者：
Okano, Hideyuki
中科院分区：
文献类型：
--
作者：
Ozawa, Yoko;Nakao, Keiko;Okano, Hideyuki
细胞因子信号转导抑制因子3（SOCS 3）是一种细胞内的，配体诱导的STAT 3激活的负反馈调节剂，在炎症过程中发挥作用。在此，我们证明SOCS 3表达对围产期视网膜正常发育是重要的。STAT 3在胚胎晚期视网膜中高度活化，然后在出生后0天（PO）下调，推测是通过上游配体的耗尽。我们发现PO后需要SOCS 3来关闭剩余的STAT 3激活;这种激活的STAT 3的丧失导致视紫红质表达和视杆细胞分化。SOCS 3缺陷不能终止STAT 3激活，从而延迟视紫红质及其上游转录因子crx的表达。后来继续发展，但其进程在时间上不稳定，可能是因为补偿不当。有趣的是，SOCS 3蛋白表达首先在出生后检测到，在STAT 3激活大部分下调之后。它最初出现在一些假定的感光细胞中，并逐渐扩散。SOCS 3 mRNA水平从胚胎晚期到出生后早期是恒定的。SOCS 3蛋白表达的转录后抑制在晚期胚胎发生期间维持高的STAT 3活化，并且在PO之后，从抑制释放迅速终止STAT 3活化。因此，SOCS 3可以在感光细胞分化期间充当STAT 3激活的时间微调器。(c)2006年爱思唯尔公司All rights reserved.
Suppressor of cytokine signaling 3 (SOCS3) is an intracellular, ligand-induced negative feedback modulator of STAT3 activation that acts during inflammation. Here, we dernonstrate that SOCS3 expression is important for normal retinal development in the perinatal period. STAT3 is highly activated in the late-embryonic retina, then downregulated at postnatal day 0 (PO), presumably by the depletion of upstream ligands. We found that SOCS3 was required after PO to shut down the residual STAT3 activation; this loss of activated STAT3 leads to Rhodopsin expression and rod photoreceptor cell differentiation. SOCS3 deficiency failed to terminate STAT3 activation, thereby delaying expression of Rhodopsin and its upstream transcription factor, crx. Development subsequently continued, but its course was temporally erratic, probably because of faulty compensation. Interestingly, SOCS3 protein expression was first detected postnatally, after STAT3 activation was mostly downregulated. It initially appeared in some of the presumptive photoreceptor cells and gradually spread. SOCS3 mRNA level was constant from the late-embryonic to early-postnatal period. Post-transcriptional inhibition of SOCS3 protein expression maintains a high STAT3 activation during late embryogenesis, and after PO, releasing from the inhibition promptly terminates STAT3 activation. Thus, SOCS3 can act as a temporal fine-tuner of STAT3 activation during photoreceptor cell differentiation. (c) 2006 Elsevier Inc. All rights reserved.