scholarly journals Bone morphogenetic protein 2 signaling in osteoclasts is negatively regulated by the BMP antagonist, twisted gastrulation

2011 ◽  
Vol 112 (3) ◽  
pp. 793-803 ◽  
Author(s):  
Lan Pham ◽  
Kayla Beyer ◽  
Eric D. Jensen ◽  
Julio Sotillo Rodriguez ◽  
Julia Davydova ◽  
...  
Keyword(s):  
Bone Morphogenetic Protein ◽  
Bone Morphogenetic Protein 2 ◽  
Twisted Gastrulation ◽  
Morphogenetic Protein ◽  
Bmp Antagonist

scholarly journals Potentiation of Astrogliogenesis by STAT3-Mediated Activation of Bone Morphogenetic Protein-Smad Signaling in Neural Stem Cells

2007 ◽  
Vol 27 (13) ◽  
pp. 4931-4937 ◽  
Author(s):  
Shinji Fukuda ◽  
Masahiko Abematsu ◽  
Hiroyuki Mori ◽  
Makoto Yanagisawa ◽  
Tetsushi Kagawa ◽  
...  
Keyword(s):  
Stem Cells ◽  
Neural Stem Cells ◽  
Bone Morphogenetic Protein ◽  
Negative Regulator ◽  
Bone Morphogenetic Protein 2 ◽  
Cytokine Signaling ◽  
Morphogenetic Protein ◽  
Regulatory Loop ◽  
Bmp Antagonist

ABSTRACT Astrocytes play important roles in brain development and injury response. Transcription factors STAT3 and Smad1, activated by leukemia inhibitory factor (LIF) and bone morphogenetic protein 2 (BMP2), respectively, form a complex with the coactivator p300 to synergistically induce astrocytes from neuroepithelial cells (NECs) (K. Nakashima, M. Yanagisawa, H. Arakawa, N. Kimura, T. Hisatsune, M. Kawabata, K. Miyazono, and T. Taga, Science 284:479-482, 1999). However, the mechanisms that govern astrogliogenesis during the determination of the fate of neural stem cells remain elusive. Here we found that LIF induces expression of BMP2 via STAT3 activation and leads to the consequent activation of Smad1 to efficiently promote astrogliogenic differentiation of NECs. The BMP antagonist Noggin abrogated LIF-induced Smad1 activation and astrogliogenesis by inhibiting BMPs produced by NECs. NECs deficient in suppressor of cytokine signaling 3 (SOCS3), a negative regulator of STAT3, readily differentiated into astrocytes upon activation by LIF not only due to sustained activation of STAT3 but also because of the consequent activation of Smad1. Our study suggests a novel LIF-triggered positive regulatory loop that enhances astrogliogenesis.

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