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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.
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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
Neurogenesis Neuronal migration Axon pathfinding Synapse formation Key steps in the development of neural network
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…”
First Author Forum Netrins Shh NTs Netrins Semaphorins Slits
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…”
First Author Forum Genetic evidences GEFs GAPs Cdc42 Rac RhoA VASP Pak ROCK LOF GOF Axon pathfinding errors
First Author Forum Models for Rho GTPase functions in growth cone guidance.
First Author Forum Conclusions: 1 Rho GTPases mediator 2 cAMP switch 3 crosstalk through myosin
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)
First Author Forum Mediator Hypothesis BDNF ——› Ca2+——›Cdc42 ——›Attraction ? LPA ——› Ga12/13——›RhoA——›Repulsion ?
The Housekeeping Technique Growth cone turning assay (Poo assay)
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
Materials and methods First Author Forum
Results First Author Forum
Results First Author Forum
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.
Results First Author Forum ……………………………………..… LPA
First Author Forum 2001/5/13 Submission to Cell
Results First Author Forum
First Author Forum 2001/12/06 Resubmission to Cell
First Author Forum 2002/4/30 Submission to Neuron
First Author Forum 2002/6/24 Submission to NCB
First Author Forum 2002/10/22 Resubmission to NCB
First Author Forum Conclusions: 1 Instructive role 2 cAMP switch 3 crosstalk through myosin
First Author Forum Implications: 1 Axon guidance signaling 2 Nerve regeneration 3 Synapse plasticity
First Author Forum Lessons: comprehensive Things should be made as simple as possible,but not any simpler Albert Einstein
First Author Forum Lessons:
First Author Forum Lessons:
First Author Forum Lessons:
First Author Forum Lessons:
First Author Forum Lessons: Don’t make a comprehensive story. Don’t evade the most important experiment.
First Author Forum Questions remain to be clarified: 1 Signaling pathway for growth cone turning 2 Who guides the expression of guidance cues?
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 !
