Nature Neuroscience
8, 616 - 625 (2005)
Published online: 24 April 2005; | doi:10.1038/nn1440
A positive autoregulatory loop of Jak-STAT signaling controls the onset of astrogliogenesisFei He1, 3, Weihong Ge1, 3, Keri Martinowich1, 3, Sara Becker-Catania3, 5, Volkan Coskun1, 3, Wenyu Zhu1, 3, Hao Wu1, 3, Diogo Castro4, Francois Guillemot4, Guoping Fan2, Jean de Vellis3
& Yi E Sun1, 31
Departments of Molecular & Medical Pharmacology and Psychiatry & Behavioral Sciences, Neuropsychiatric Institute, University of California Los Angeles, Los Angeles, California 90024, USA. 2
Department of Human Genetics, David Geffen School of Medicine, Neuropsychiatric Institute, University of California Los Angeles, Los Angeles, California 90024, USA. 3
Mental Retardation Research Center, Neuropsychiatric Institute, University of California Los Angeles, Los Angeles, California 90024, USA. 4
Division of Molecular Neurobiology, National Institute for Medical Research, Mill Hill, London NW7 1AA, UK. 5
Present address: Edward Hines Veterans Administration Hospital, University of Illinois at Chicago, Hines, Illinois 60141, USA.
Correspondence should be addressed to Yi E Sun ysun@mednet.ucla.eduDuring 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.
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