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Rho GTPases: PowerPoint Presentation
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Rho GTPases:

Rho GTPases:

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Rho GTPases:

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  1. First Author Forum Rho GTPases: halfway island from gene to circuit Xiao-bing Yuan Neural Plasticity Group Institute of Neuroscience Shanghai Institutes of Biological Sciences Chinese Academy of Science

  2. Neurogenesis Neuronal migration Axon pathfinding Synapse formation Key steps in the development of neural network

  3. First Author Forum Growth cone “appears to insinuate themselves between the surrounding elements, relentlessly forging a path through the interstitial matrix.” It “endowed with amoeboid movements. It could be compared to a living battering ram, soft and flexible, which advances, pushing aside mechanically the obstacles which it finds in its way, until it reaches the area of its peripheral distribution.” Cajal’s drawing Guide Post “This fiber ends … in an enlargement which may be rounded and subtle, but that may also adopt a conical appearance. This latter we shall name the growth cone, that at times displays fine and short extensions…”

  4. First Author Forum Netrins Shh NTs Netrins Semaphorins Slits

  5. Cajal’s drawing Growth cone “appears to insinuate themselves between the surrounding elements, relentlessly forging a path through the interstitial matrix.” It “endowed with amoeboid movements. It could be compared to a living battering ram, soft and flexible, which advances, pushing aside mechanically the obstacles which it finds in its way, until it reaches the area of its peripheral distribution.” “This fiber ends … in an enlargement which may be rounded and subtle, but that may also adopt a conical appearance. This latter we shall name the growth cone, that at times displays fine and short extensions…”

  6. First Author Forum ? Receptor Cytoskeleton

  7. First Author Forum Rho GTPases

  8. First Author Forum Rho GTPases

  9. First Author Forum Genetic evidences GEFs GAPs Cdc42 Rac RhoA VASP Pak ROCK LOF GOF Axon pathfinding errors

  10. First Author Forum Cdc42/Rac1/ RhoA

  11. First Author Forum How ? Instructive or permissive ?

  12. First Author Forum Models for Rho GTPase functions in growth cone guidance.

  13. First Author Forum Conclusions: 1 Rho GTPases mediator 2 cAMP switch 3 crosstalk through myosin

  14. First Author Forum This is a fairly comprehensive study of Rho GTPase involvement in axonal turning in the Xenopus spinal cord. (Guan & Rao Nature Review Neuroscience, 2003)

  15. First Author Forum Mediator Hypothesis BDNF ——› Ca2+——›Cdc42 ——›Attraction ? LPA ——› Ga12/13——›RhoA——›Repulsion ?

  16. The Housekeeping Technique Growth cone turning assay (Poo assay)

  17. Materials and methods First Author Forum cDNA two-cell stage dissociation Stage 22 Select cells with GFP fluorescence 14 - 20 hr rt Turning Assay Fertilized egg

  18. Materials and methods First Author Forum

  19. Results First Author Forum

  20. Results First Author Forum

  21. Results First Author Forum LPA ··············································································· -15 -10 -5 0 5 10 15 20 25 30 Y-27632 LPA ··············································································· ·················································································································· -15 -10 -5 0 5 10 15 20 25 30 Figure 5. RhoA- and ROCK-dependent neurite inhibition or collapse induced by LPA.

  22. Results First Author Forum ……………………………………..… LPA

  23. First Author Forum

  24. First Author Forum 2001/5/13 Submission to Cell

  25. Results First Author Forum

  26. First Author Forum

  27. First Author Forum

  28. First Author Forum 2001/12/06 Resubmission to Cell

  29. First Author Forum

  30. First Author Forum 2002/4/30 Submission to Neuron

  31. First Author Forum 2002/6/24 Submission to NCB

  32. First Author Forum

  33. First Author Forum

  34. First Author Forum 2002/10/22 Resubmission to NCB

  35. First Author Forum Conclusions: 1 Instructive role 2 cAMP switch 3 crosstalk through myosin

  36. First Author Forum Implications: 1 Axon guidance signaling 2 Nerve regeneration 3 Synapse plasticity

  37. First Author Forum Lessons: comprehensive Things should be made as simple as possible,but not any simpler Albert Einstein

  38. First Author Forum Lessons:

  39. First Author Forum Lessons:

  40. First Author Forum Lessons:

  41. First Author Forum Lessons:

  42. First Author Forum Lessons: Don’t make a comprehensive story. Don’t evade the most important experiment.

  43. First Author Forum Questions remain to be clarified: 1 Signaling pathway for growth cone turning 2 Who guides the expression of guidance cues?

  44. First Author Forum Acknowledgement Prof. Mu-Ming Poo Dr. Yu- Qinag Ding Prof. Shumin Duan Dr. Yi-Zheng Wang Prof. Chienping Wu Dr. Xue-Liang Zhu Dr. Guo-Li Ming Dr. Gang Pei Dr. Lin-Ying Feng Ming Jin Xiao-Hua Xu Rotation students Thanks !