Turnley Ann M, Faux Clare H, Rietze Rodney L, Coonan Jason R, Bartlett Perry F
The Walter and Eliza Hall Institute of Medical Research, P.O. Royal Melbourne Hospital, Melbourne, Victoria 3050, Australia.
Nat Neurosci. 2002 Nov;5(11):1155-62. doi: 10.1038/nn954.
The intracellular mechanisms that determine the response of neural progenitor cells to growth factors and regulate their differentiation into either neurons or astrocytes remain unclear. We found that expression of SOCS2, an intracellular regulator of cytokine signaling, was restricted to mouse progenitor cells and neurons in response to leukemia inhibitory factor (LIF)-like cytokines. Progenitors lacking SOCS2 produced fewer neurons and more astrocytes in vitro, and Socs2(-/-) mice had fewer neurons and neurogenin-1 (Ngn1)-expressing cells in the developing cortex, whereas overexpression of SOCS2 increased neuronal differentiation. We also report that growth hormone inhibited Ngn1 expression and neuronal production, and this action was blocked by SOCS2 overexpression. These findings indicate that SOCS2 promotes neuronal differentiation by blocking growth hormone-mediated downregulation of Ngn1.
决定神经祖细胞对生长因子的反应并调节其分化为神经元或星形胶质细胞的细胞内机制仍不清楚。我们发现，细胞因子信号传导的细胞内调节因子SOCS2的表达，在白血病抑制因子（LIF）样细胞因子的作用下，局限于小鼠祖细胞和神经元。缺乏SOCS2的祖细胞在体外产生的神经元较少，星形胶质细胞较多，并且Socs2(-/-)小鼠在发育中的皮质中神经元和表达神经生成素-1（Ngn1）的细胞较少，而SOCS2的过表达增加了神经元分化。我们还报告说，生长激素抑制Ngn1表达和神经元生成，并且这种作用被SOCS2过表达所阻断。这些发现表明，SOCS2通过阻断生长激素介导的Ngn1下调来促进神经元分化。
