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The First Author Forum ION LiYan

The First Author Forum ION LiYan. Axon Guidance: an intriguing question from 100 years ago. Chemotaxis mechanism for axon guidance. Santiago Ramón y Cajal. Adapted from Nobel Lecture 1906,.

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The First Author Forum ION LiYan

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  1. The First Author Forum ION LiYan Axon Guidance: an intriguing question from 100 years ago Chemotaxis mechanism for axon guidance Santiago Ramón y Cajal Adapted fromNobel Lecture 1906, “From the functional point of view the growth cone may be regarded as a sort of club or battering ram, endowed with exquisite chemical sensitivity, with rapid ameboid movements, and with certain impulsive force, thanks to which it is able to proceed forward and overcome obstacles met in its way, forcing cellular interstices until it arrives at its destination”

  2. The First Author Forum ION LiYan Ross Granville Harrison • First observed growth cone movement of neurons growing in tissue culture • Contact guidance mechanism J. Exp. Zool., 9:787–846 (1910).

  3. The First Author Forum ION LiYan The model systems of studying the axon guidance In vivo Vertebrate ventral spinal cord Optic chiasm Drosophila ventral nerve cord In vitro Explant culture Turning assay

  4. The First Author Forum ION LiYan The model systems of studying the axon guidance In vivo vertebrate ventral spinal cord Cell, Vol. 87, 1001–1014, December 13, 1996,

  5. The First Author Forum ION LiYan The model systems of studying the axon guidance In vivo Optic chiasm Cell, Vol. 119, 567–578, November 12, 2004,

  6. The First Author Forum ION LiYan The model systems of studying the axon guidance In vivo Drosophila ventral nerve cord Nat Neurosci. 2005 Feb;8(2):156-63, Jan 16, 2005

  7. The First Author Forum ION LiYan The model systems of studying the axon guidance In vitro Explant culture Cell, Vol. 96, 807–818, March 19, 1999,

  8. The First Author Forum ION LiYan The model systems of studying the axon guidance In vitro Turning assay

  9. The First Author Forum ION LiYan Why did we choose cerebellar granule cells?

  10. The First Author Forum ION LiYan How did I modify the turning assay? New information Collaboration

  11. The First Author Forum ION LiYan Basic question in the axon guidance 1. Finding the new guidance cues 2. Mechanism of axon guidance induced by guidance cues Ca2+ signal Cytoskeletal dynamics

  12. The First Author Forum ION LiYan Repeat the classic experiments with the new technique to find the novel and undiscovered phenomena Directly touch the key problems undiscovered and unsolved by others in the field Cajal 1891 Nature,Vol. 399, 6 May, 1999 How to find the question? • Read the text book 2. Read the newest review in the field

  13. The First Author Forum ION LiYan 2003 SARS Why BDNF? • Mice lacking brain-derived neurotrophic factor develop with sensory deficits • Ernfors P, Lee KF, Jaenisch R. • Nature. 1994 Mar 10;368(6467):147-50 • cAMP-induced switching in turning direction of nerve growth cones • Song HJ, Ming GL, Poo MM • Nature. 1997 Jul 17;388(6639):275-9 • BDNF stimulates migration of cerebellar granule cells. • Borghesani PR, Peyrin JM, Klein R, Rubin J, Carter AR, Schwartz PM, Luster A, Corfas G, Segal RA • Development. 2002 Mar;129(6):1435-42

  14. The First Author Forum ION LiYan Turning response induced by BDNF is dependent on both intracellular Ca2+ and extracellular Ca2+ How to enter the growth cone?

  15. The First Author Forum ION LiYan Calcium signalling in the guidance of nerve growth by netrin-1 Kyonsoo Hong*², Makoto Nishiyama*², John Henley*, Marc Tessier-Lavigne³ & Mu-ming Poo* NATURE |VOL 403 | 6 JANUARY 2000 The netrin-1-induced turning response depends on Ca2+ influx through plasma membrane L-type Ca2+ channels, as well as Ca2+- induced Ca2+ release from cytoplasmic stores.

  16. The First Author Forum ION LiYan L-Type Ca2+ Channel? Voltage-dependent Ca2+ Channels (VDCCs)

  17. The First Author Forum ION LiYan • Neurotrophin-evoked depolarization requires the sodium channel Na(V)1.9. • Neurotrophin-evoked rapid excitation through TrkB receptors • Blum R, Kafitz KW, Konnerth A. • Kafitz KW, Rose CR, Thoenen H, Konnerth A. Nature. 2002 Oct 17;419(6908):687-93. Nature. 1999 Oct 28;401(6756):918-21

  18. The First Author Forum ION LiYan Hypothesis I: BDNF Nav1.9Channel Depolarize membrane VDCCs Ca2+ entry

  19. The First Author Forum ION LiYan Our Study

  20. The First Author Forum ION LiYan Ca2+ dependent chemoattraction induced by BDNF

  21. The First Author Forum ION LiYan Novel Ca2+ entery mechenisam in the turning induced by BDNF

  22. The First Author Forum ION LiYan Activation of a TRPC3-Dependent Cation Current through the Neurotrophin BDNF Hong-Sheng Li, Xian-Zhong Shawn Xu, and Craig Montell* Neuron, Vol. 24, 261–273, September, 1999, Hypothesis II: BDNF TRP Channel Ca2+ entry

  23. The First Author Forum ION LiYan TRP channels involved in the turning induced by BDNF

  24. The First Author Forum ION LiYan TRP channels mediated Ca2+ entery in the turning induced by BDNF

  25. The First Author Forum ION LiYan

  26. The First Author Forum ION LiYan Choice Breakthrough Work: Gating mechanism Solid Work: Examination Subfamily

  27. The First Author Forum ION LiYan The expression of TRPC channels in the cerebellar granule cells

  28. The First Author Forum ION LiYan TRPC3/6 channels were essential for the BDNF- induced attraction

  29. The First Author Forum ION LiYan TRPC3/6 channels were essential for the BDNF- induced Ca2+ signal

  30. The First Author Forum ION LiYan Model Nature, Vol. 434, 14 April 2005

  31. The First Author Forum ION LiYan choice How to finish your project efficiently? 1. Understand the question which you are working on 2. Modify your hypothesis based on your data 3. Work independently 4. Push your PI instead of being pushed

  32. The First Author Forum ION LiYan My strategy to find a project in the lab • Based on the technique in the lab • Hypothesis driven • Used and developed new technique based on the experiments

  33. The First Author Forum ION LiYan The better way for junior students to begin the project 1. Think about the big problem unsolved in your field 2. Peer the ongoing project and research interest in your lab 3. Open your mind 4. Accumulate the experimental experience 5. Analyze your data in time

  34. The First Author Forum ION LiYan It is harmful to wait for your PI arranging everything for you!

  35. The First Author Forum ION LiYan The most important thing for us Interest Persistence

  36. The First Author Forum ION LiYan Thanks!

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