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MIT 7 72 - Steps in Development

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17.729.6.06Introduction(Steps in Development)ModelorganismsAnalysis PrinciplesGrowth controlHuman issuesOrganformationStemcellsAxon guidanceFoundations+ +Developmental Readout3DstructureAxes2ModelorganismsAnalysis PrinciplesNervousSystemHuman issuesCloningStemcellsOrganFormationFoundations+ +Developmental Readout3DstructurePostionalinformation1. Development occursover time and in 3D3+=egg spermzygote embryoadult organismhuman ~1014 cellsfertilizationreplacementcells1timeTeratogen: Effects of thalidomide on limb formation24Normal brain Fetal Alcohol Syndrome brain3Newt limb regenerationamputation455662. Multiple processesdirect developmentCell division: human embryos from 24 days (stage 11) >>> 56 days (stage 23) after fertilization77Chick and Duck feet show differential cell death (apoptosis)8Cell type and tissue: eye/ retinal neurons98dorsalventraldorsal (back)ventral (belly)anterior(head)posterior(tail)Defining positionThe axesleft right103D structure:heart119Zebrafish development 1-19 hours post fertilization12Watch for:1.Cell division2.Structure3. Cell fate requiresdifferentialgene expression10Gene Intermediate(can be final product) Final productGene expression = formation of final product13ErythrocytesNeuronsSpermatozoaCell types aredifferent becausethey makedifferent proteins1411(determined)timeH. Sive MIT 200615(determined)timeH. Sive MIT 20061512Regulatory genesErythrocyte Neuron SpermGene expressionA combinatorial regulatory code controls cell typeCell typeCell-type specific factorsGeneral factorsRestricted factorsR,F,KH. Sive MIT 200616A,I,K A,F,KOne set of regulatory genes activatesmany differentiation genesR, F, K1, 2, 3, 4, ……… 100 Regulatory code for erythrocytes= genes required for commitmentDifferentiation code for erythrocytes= genes required for final functionH. Sive MIT 20061713transcriptioninitiation or terminationRNA splicing, stability or exporttranslation initiationor elongation nucleusexport to cytoplasmgeneRegulatory genes control gene expression at many stepsprotein trafficking,modification or stabilityH. Sive MIT 2006184. Complexity increaseswith developmental age14Increasing complexity of the future eye19eggetcspermone territorytwo territoriesthree territoriesfive territoriesone celltwo cellsfour cellseight cellsIncreasing complexityduring developmentEach territoryhas a particularregulatory codeH. Sive MIT 200620155. Regulatory factors actwithin or between cellsDETERMINANTSCells become different because of what they inherit.Cell with localized regulators called “determinants”divides+Cell type 1 Cell type 2timeH. Sive MIT 20062116zygote two cell32 cellDAPI/ nucleiFluorescence/ P-granulesDeterminants: P-granules >> future germ cells in C. elegans22cells secrete an “inducer”= ligand INDUCTION Cells become different because their neighbors tell them to do so.timeand changescell fate“cell-cell signaling”which bindsto receptors on target cells, activates signal transduction Cell type 1H. Sive MIT 20062317Induction in the sea urchin: micromeres induce animal cells24Delta protein is found in inducing micromeres2518An inducer that can induce different fatesat different concentrations is termed a“morphogen”timeCell type 1timeCell type 2H. Sive MIT 200626eggetcspermone territorytwo territoriesthree territoriesfive territoriesone celltwo cellsfour cellseight cellsdeterminantinducerdeterminantsand inducersincrease complexity of the embryoH. Sive MIT 20062719(determined)H. Sive MIT


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