Abstract
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.
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Acknowledgements
We would like to thank A. Voss for advice with stereology and M. Ransome for technical assistance. This work was supported by the NH and MRC of Australia, the CRC for Cellular Growth Factors, the Australasian Spinal Research Trust, the Motor Neurone Disease Research Institute of Australia, ANZ Charitable Trusts, the Clive and Vera Ramaciotti Foundation for Biomedical Research and the BHP Community Trust.
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Turnley, A., Faux, C., Rietze, R. et al. Suppressor of cytokine signaling 2 regulates neuronal differentiation by inhibiting growth hormone signaling. Nat Neurosci 5, 1155–1162 (2002). https://doi.org/10.1038/nn954
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DOI: https://doi.org/10.1038/nn954
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