@article{76a500a748c14bfbafa4d0cded5cf640,
title = "A positive autoregulatory loop of Jak-STAT signaling controls the onset of astrogliogenesis",
abstract = "During development of the CNS, neurons and glia are generated in a sequential manner. The mechanism underlying the later onset of gliogenesis is poorly understood, although the cytokine-induced Jak-STAT pathway has been postulated to regulate astrogliogenesis. Here, we report that the overall activity of Jak-STAT signaling is dynamically regulated in mouse cortical germinal zone during development. As such, activated STAT1/3 and STAT-mediated transcription are negligible at early, neurogenic stages, when neurogenic factors are highly expressed. At later, gliogenic periods, decreased expression of neurogenic factors causes robust elevation of STAT activity. Our data demonstrate a positive autoregulatory loop whereby STAT1/3 directly induces the expression of various components of the Jak-STAT pathway to strengthen STAT signaling and trigger astrogliogenesis. Forced activation of Jak-STAT signaling leads to precocious astrogliogenesis, and inhibition of this pathway blocks astrocyte differentiation. These observations suggest that autoregulation of the Jak-STAT pathway controls the onset of astrogliogenesis.",
author = "Fei He and Weihong Ge and Keri Martinowich and Sara Becker-Catania and Volkan Coskun and Wenyu Zhu and Hao Wu and Diogo Castro and Francois Guillemot and Guoping Fan and {De Vellis}, Jean and Sun, {Yi E.}",
note = "Funding Information: We would like to thank L. Zipursky, H. Herschman and K. Shuai at UCLA for critical reading of the manuscript and providing suggestions, and L. Hutnick at UCLA for cloning the S100b promoter. We would like to acknowledge J. Wong (Baylor College of Medicine), J.E. Johnson (University of Texas Southwestern), D. Levy (New York University), K. Shuai (University of California at Los Angeles), J.E. Darnell, Jr. (Rockefeller University), J. Bromberg (Memorial Sloan-Kettering Cancer Center) and S.C. Landis (National Institute of Neurological Disorders and Stroke) for sharing critical reagents. This work is supported by National Institutes of Health (NIH) RO1 grant (MH066196), a Beckman Young Investigator Award, a Sloan Research Fellowship, a Klingenstein award and a National Alliance for Research on Schizophrenia and Depression award to Y.E.S., NIH program project grant (HD006576) to J.d.V. and Y.E.S. and NIH NS44405 to G.F.",
year = "2005",
month = may,
doi = "10.1038/nn1440",
language = "English (US)",
volume = "8",
pages = "616--625",
journal = "Nature Neuroscience",
issn = "1097-6256",
publisher = "Nature Publishing Group",
number = "5",
}