期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 108, 期 29, 页码 12119-12124出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1100160108
关键词
intermediate zone; neurogenesis
资金
- Strategic Priority Research Program of the Chinese Academy of Sciences [XDA01010201]
- National Natural Science Foundation of China [30830034, 90919046]
- National Key Basic Research and Development Program of China [2007CB947101, 2008KR0695, 2009CB941100]
- Shanghai Key Project of Basic Science Research [08DJ1400501]
- Council of Shanghai Municipal Government for Science and Technology [088014199]
- MRC [MC_U117570528] Funding Source: UKRI
- Medical Research Council [MC_U117570528] Funding Source: researchfish
Proliferation of the neural/neuronal progenitor cells (NPCs) at the ventricular zone of the dorsal spinal cord requires the stimuli of Wnt and bone morphogenic protein (BMP). However, how these two signaling pathways are regulated to initiate differentiation in the NPCs as they enter the intermediate zone is not known. Here, we show that Smad6, a negative regulator of BMP signaling, is expressed in the intermediate zone of the chick dorsal spinal cord. Knockdown experiments show that Smad6 is required for promoting NPCs to exit the cell cycle and differentiate into neurons. Although we find that Smad6 inhibits BMP signaling, as expected, we also find that Smad6 unexpectedly inhibits the Wnt/beta-catenin pathway. The inhibition of the Wnt/beta-catenin pathway by Smad6 is independent of its effect on the BMP pathway. Rather, Smad6 through its N-terminal domain and link region enhances the interaction of C-terminal binding protein with the beta-catenin/T cell factor (TCF) complex and the TCF-binding element to inhibit beta-cateninmediated transcriptional activation. Our study provides evidence that transition of NPCs from a proliferative state to a differentiating state is controlled by the dual inhibitory role of Smad6 to both BMP and Wnt signaling at the level of transcription.
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