袁小兵 博士 神经回路发育的分子机制研究
袁小兵 博士 神经回路发育的分子机制研究
My major research findings include the clarification of basic mechanisms underlying the signal transduction of axon pathfinding and neuronal migration. My collaborators and I discovered a signal transduction pathway from Ca2+ to Rho-GTPase as an important intracellular mediator for axon pathfinding. My team also demonstrated that guidance factors that induce the Ca2+ signals at the axonal growth cone achieve their guidance functions via the activation of TRPC channels, which were previously known to mediate pain, thermal, and mechanical sensation. In recent years, I have focused on guidance of the radial migration of cortical neurons by diffusible guidance factors and the intracellular molecular machineries that drive neuron migration. My team discovered that a long-distance signal transduction from the leading tip toward the neuronal soma, in the form of a propagating Ca2+ wave, directs a coordinated global motility response in migratory neurons when they encounter an extracellular repulsive signal. We also discovered that the leading growth cone of migrating neurons can generate the traction force to pull the rest of the neuron forward through a myosin-dependent forward flow of cortical F-actins along the leading neurite, and we proposed a “front-pulling” model of neuronal migration.
My current research interests include (i) studying how cadherin family members contribute to the normal development of brain circuitries that are closely relevant to autism and clarifying what signaling pathway mediates their function, (ii) exploring the role of non-coding elements in brain development and disorder, and (iii) clarifying the function of several newly-identified autism genes and how mutation of these genes leads to autism.
2001年在中国科学院神经科学研究所获得理学博士学位，2001-2012年在中科院神经科学研究所工作，2012至今担任脑功能基因组学教育部重点实验室PI。多篇论文发表在Nature、Cell 、Neuron等顶级科研杂志上， 曾获得中国“杰出青年基金”（2006年）、第9届中国青年科技奖（2007年）、上海市自然科学一等奖（2013年）等多项奖励。
1. Zhao PP, Yao MJ, Chang SY, Gou LT, Liu MF, Qiu ZL, Yuan XB*. Novel function of PIWIL1 in neuronal polarization and migration via regulation of microtubule-associated proteins. cells. Mol. Brain doi: 10.1186/s13041-015-0131-0. (2015). (PMID: 26104391)
2. Yao MJ, Chen G, Zhao PP, Lu MH, Liu MF and Yuan XB*. Transcriptome analysis of microRNAs in developing cerebral cortex of rat. BMC Genomics 13:232 (2012). (PMID: 22691069)
3. Huang ZH, Wang Y, Su ZD, Geng JG, Chen YZ, Yuan XB*, He C*. Slit-2 repels the migration of olfactory ensheathing cells by triggering Ca2+-dependent Cofilin activation and RhoA inhibition. J. Cell Sci. 124：186-197 (2011). (PMID: 21187345)
4. Zheng W, Geng AQ, Li PF, Wang Y, Yuan XB*. Robo4 regulates the radial migration of newborn neurons in developing neocortex. Cerebral Cortex doi:10.1093/cercor/bhr330 (2011). (PMID: 22123939)
5. He M, Zhang ZH, Guan CB, Xia D, Yuan XB*. Leading tip drives soma translocation via forward F-actin flow during neuronal migration. J. Neurosci. 30:10885–10898 (2010). (PMID: 20702717)
6. Zhao CT, Li K, Li JT, Zheng W, Liang XJ, Geng AQ, Li N, and Yuan XB*. PKCδ regulates cortical radial migration by stabilizing the Cdk5 activator p35. PNAS. 106: 21353-21358 (2009). (PMID: 19965374)
7. Chen G, Sima J, Jin M, Zheng W, Wang KY, Xue XJ, Ding YQ, Yuan XB*. Semaphorin-3A guides radial migration of cortical neurons during development. Nature Neurosci., 11: 36-44 (2008). (PMID: 18059265)
8. Guan CB, Xu HT, Jin M, Yuan XB*, and Poo MM*. Long-range Ca2+ signaling from growth cone to soma mediates reversal of neuronal migration induced by Slit-2. Cell 129: 385-395 (2007). (PMID: 17448996)
9. Jin M, Guan CB, Jiang YA, Zhao CT, Cui K, Song YQ, Wu CP, Duan SM, Poo MM*, Yuan XB*. Ca2+-dependent regulation of Rho GTPases can trigger turning of nerve growth cones. J. Neurosci., 25: 2338-47 (2005). (PMID: 15745960)
10. Li Y, Cui K, Jia YC, Li N, Zhen ZY, Wang YZ, Yuan XB*. Essential role of TRPC channels in the guidance of nerve growth cone by BDNF. Nature, 14:835-8 (2005). (PMID: 15758952)