Interferon-gamma inhibits the neuronal differentiation of neural progenitor cells by inhibiting the expression of Neurogenin2 via the JAK/STAT1 pathway.
Interferon-gamma (IFN-γ) is one of the critical cytokines released by host immune cells upon infection. Despite the important role(s) of IFN-γ in host immune responses, there has been no in vivo study regarding the effects of IFN-γ on brain development, and the results from many in vitro studies are controversial. In this study, the effects of IFN-γ on embryonic neurogenesis were investigated. Treatment of E14.5 mouse neural progenitor cells (NPCs) with IFN-γ resulted in a decrease in the percentage of TuJ1-positive immature neurons but an increase in the percentage of Nestin-positive NPCs. Similar results were obtained in vivo. Treatment of NPCs with a JAK inhibitor or the knockdown of STAT1 expression abrogated the IFN-γ-mediated inhibition of neurogenesis. Interestingly, the expression of one of proneural genes, Neurogenin2 (Neurog2) was dramatically inhibited upon IFN-γ treatment, and cells overexpressing Neurog2 did not respond to IFN-γ. Taken together, our results demonstrate that IFN-γ inhibits neuronal differentiation of NPCs by negatively regulating the expression of Neurog2 via the JAK/STAT1 pathway. Our findings may provide an insight into the role of IFN-γ in the development of embryonic brain.
School of Biological Sciences, Seoul National University, 504-208, Gwanak-Gu, Seoul 151-742, South Korea. Electronic address: aliceblue@snu.ac.kr.
Jyhyun
J
Ahn
School of Biological Sciences, Seoul National University, 504-208, Gwanak-Gu, Seoul 151-742, South Korea. Electronic address: 8qoo8@naver.com.
Junsub
J
Lee
School of Biological Sciences, Seoul National University, 504-208, Gwanak-Gu, Seoul 151-742, South Korea. Electronic address: sunyoung@snu.ac.kr.
Sunyoung
S
Kim
D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics* / Q000276:immunology; D002478:Cells, Cultured; D015536:Down-Regulation; D007371:Interferon-gamma / Q000276:immunology*; D053612:Janus Kinases / Q000276:immunology*; D051379:Mice; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000276:immunology; D058953:Neural Stem Cells / Q000166:cytology* / Q000276:immunology / Q000378:metabolism; D055495:Neurogenesis; D050794:STAT1 Transcription Factor / Q000276:immunology*; D015398:Signal Transduction
D051792:Basic Helix-Loop-Helix Proteins; D007371:Interferon-gamma; D053612:Janus Kinases; D009419:Nerve Tissue Proteins; D050794:STAT1 Transcription Factor; C102938:Neurog2 protein, mouse; C494080:Stat1 protein, mouse
Differentiation; Embryonic neurogenesis; Interferon gamma; Neural progenitor cells; Neurogenin2; STAT1