A positive autoregulatory loop of Jak-STAT signaling controls the onset of astrogliogenesis

Fei He, Weihong Ge, Keri Martinowich, Sara Becker-Catania, Volkan Coskun, Wenyu Zhu, Hao Wu, Diogo Castro, Francois Guillemot, Guoping Fan, Jean De Vellis, Yi E. Sun

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Pages (from-to)616-625
Number of pages10
JournalNature neuroscience
Volume8
Issue number5
DOIs
StatePublished - May 2005

ASJC Scopus subject areas

  • Neuroscience(all)

Fingerprint Dive into the research topics of 'A positive autoregulatory loop of Jak-STAT signaling controls the onset of astrogliogenesis'. Together they form a unique fingerprint.

Cite this