Suppressor of cytokine signaling 2 regulates neuronal differentiation by inhibiting growth hormone signaling.
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.
D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins; D002452:Cell Count; D002454:Cell Differentiation / Q000502:physiology; D002478:Cells, Cultured; D004268:DNA-Binding Proteins; D018507:Gene Expression Regulation, Developmental; D013006:Growth Hormone / Q000378:metabolism / Q000494:pharmacology*; D006131:Growth Inhibitors / Q000378:metabolism / Q000494:pharmacology; D015850:Interleukin-6; D053605:Leukemia Inhibitory Factor; D053680:Leukemia Inhibitory Factor Receptor alpha Subunit; D008222:Lymphokines / Q000378:metabolism / Q000494:pharmacology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D039902:Multipotent Stem Cells / Q000166:cytology / Q000502:physiology; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D009474:Neurons / Q000166:cytology* / Q000502:physiology; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D018121:Receptors, Cytokine / Q000378:metabolism; D053606:Receptors, OSM-LIF; D012097:Repressor Proteins; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D050826:Suppressor of Cytokine Signaling Proteins; D015534:Trans-Activators; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation / Q000502:physiology
D051792:Basic Helix-Loop-Helix Proteins; D004268:DNA-Binding Proteins; D013006:Growth Hormone; D006131:Growth Inhibitors; D015850:Interleukin-6; D053605:Leukemia Inhibitory Factor; D053680:Leukemia Inhibitory Factor Receptor alpha Subunit; D008222:Lymphokines; D009419:Nerve Tissue Proteins; D011506:Proteins; D018121:Receptors, Cytokine; D053606:Receptors, OSM-LIF; D012097:Repressor Proteins; D050826:Suppressor of Cytokine Signaling Proteins; D015534:Trans-Activators; D014157:Transcription Factors; C507838:Lif protein, mouse; C507841:Lifr protein, mouse; C491409:Socs2 protein, mouse; C486336:Neurog1 protein, mouse