Apoptosis and Senescence

Experiment remove chick limb bud from one side of

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Experiment : Remove chick limb bud from one side of animal Quantify motor neurons in both sides of chick embryos Amputated side has 80% less motor neurons than intact side Compare neuron production at early stage vs. neuron survival at later stage to show if it is the birth of neurons or the survival of neurons that is affected An intact limb bud is necessary for motor neuron survival 6
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7 Apoptosis regulated neuron number Conclusion: Limb bud produces something that promotes neuron survival Motor neuron number determined by the “field” they will innervate Question : Is an additional limb bud sufficient to promote motor neuron survival? Experiment : Transplant extra chick limb bud to one side of embryo Quantify motor neurons in both sides of chick embryos Transplanted side has 50% more motor neurons than unmanipulated side Compare neuron production at early stage vs. neuron survival at later stage to show if it is the birth of neurons or the survival of neurons that is affected An ectopic limb bud is sufficient to increase motor neuron survival
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Trophic Factors promote cell survival Trophic Factors- secreted ligands Neurotrophins- neuronal trophic factors Trk Receptors- RTK in neurons that bind to neurotrophins Ligand-Receptor pairs are active in certain neuron-target tissues---> survival of specific neurons in specific tissues Loss of ligand or receptor results in similar phenotype Loss of skin sensory neurons Loss of muscle sensory neurons 8 Examples of Ligand/Receptor Pairs NGF/TrkA skin sensory neurons NT-3/TrkC muscle sensory neurons
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Trophic Factors activate PI3K signal transduction 9 No Ligand= Apoptosis Plus Ligand= Survival
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Trophic Factors activate PI3K signal transduction 10
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Trophic Factors activate PI3K signal transduction 11 No Ligand= Apoptosis Plus Ligand= Survival
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C.elegans as a model of apoptosis Caenorhabditis elegans Transparent worm All cell fates are known (947 generated; 131 cells die) Genome completed Established forward and reverse genetic systems 12 Wild Type Apoptosis-defective
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