Proliferation of the neural/neuronal progenitor cells (NPCs) at the ventricular zone of the dorsal spinal cord requires the stimuli of Wnt and BMP. How these two signaling pathways are regulated in the NPCs as they enter the intermediate zone (IZ) to initiate differentiation is not known. Recently, a team of researchers, led by JING Naihe, at the Institute of Biochemistry and Cell Biology（SIBCB）, Shanghai Institutes for Biological Sciences, CAS, found that Smad6, a negative regulator of BMP signaling, was expressed in the IZ of the chick dorsal spinal cord and promoted NPCs to exit cell cycle and differentiate into neurons.

XIE Zhihui, CHEN Yongfeng and their colleagues at Prof. JING's lab found that Smad6 inhibited the BMP signaling as well as the Wnt/β-catenin pathway to promote neuronal differentiation. The inhibition of the Wnt/β-catenin pathway by Smad6 is independent of its effect on the BMP pathway. Rather, Smad6 enhanced the interaction of C-terminal binding protein (CtBP) with the β-catenin/TCF4 complex to inhibit β-catenin mediated transcriptional activation. This study provided evidence that transition of NPCs from a proliferative state to a differentiating state was controlled by the dual inhibitory role of Smad6 to both BMP and Wnt signaling at the level of transcription. This work entitled "Smad6 promotes neuronal differentiation in the intermediate zone of the dorsal neural tube by inhibition of the Wnt/β-catenin pathway" was published online in Proceedings of the National Academy of Sciences on July 5th, 2011.

This study was supported by the grants from the "Strategic Priority Research Program" of the Chinese Academy of Sciences, National Natural Science Foundation of China, National Key Basic Research and Development Program of China, Shanghai Key Project of Basic Science Research, and the Science and Technology Commission of Shanghai Municipal Government . (SIBCB)