bicd130_06_lecture12r

bicd130_06_lecture12r - BICD 130 Embryos, Genes, and...

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Unformatted text preview: BICD 130 Embryos, Genes, and Development Cell Fate Specification Autonomous: Depends on factors inherited by, or expressed in, the cell itself Conditional: Depends on external influences (cell-cell signaling) Cell Fate Specification Autonomous: Depends on factors inherited by, or expressed in, the cell itself Conditional: Depends on external influences (cell-cell signaling) A handful of cell-cell signaling pathways control the great majority of conditional cell fate specification events in animal development Key Cell-Cell Signaling Pathways in Development TGF- /Activin/BMP Hedgehog Wnt Notch RTK/Ras/ERK JAK/STAT A generic signal transduction pathway for development Key Cell-Cell Signaling Pathways in Development TGF- /Activin/BMP Hedgehog Wnt Notch RTK/Ras/ERK JAK/STAT The TGFsuperfamily of secreted signaling molecules includes the BMPs, activins, and TGF- s The TGF- signal transduction pathway Key Cell-Cell Signaling Pathways in Development TGF- /Activin/BMP Hedgehog Wnt Notch RTK/Ras/ERK JAK/STAT The Hedgehog pathway In the absence of ligand, the Ci transcription factor acts as a repressor The Hedgehog pathway In the presence of ligand, the Ci transcription factor is converted to an activator Sonic hedgehog expression in the chick embryo Red: Neural tube Blue: Gut Black: Limb bud The TGF- and Hedgehog pathways collaborate to pattern the neural tube in the D/V axis Graded responses to TGF- family ligands and Sonic hedgehog define specific classes of neurons in the neural tube Cyclopia caused by ingesting inhibitors of cholesterol synthesis (jervine and cyclopamine in the plant Veratrum californicum) Cholesterol is critical for several steps of Hedgehog pathway function Key Cell-Cell Signaling Pathways in Development TGF- /Activin/BMP Hedgehog Wnt Notch RTK/Ras/ERK JAK/STAT The Wnt pathway uses -catenin as a signal transduction molecule Mutations in catenin and APC are associated with tumorigenesis Key Cell-Cell Signaling Pathways in Development TGF- /Activin/BMP Hedgehog Wnt Notch RTK/Ras/ERK JAK/STAT The intracellular domain of the Notch receptor acts as a transcriptional co-activator Sensory bristles are arrayed over the body surface of the adult fly Notch signaling distinguishes the bristle precursor and epidermal cell fates within "proneural clusters" "lateral inhibition" Proneural bHLH protein expression Interference with Notch signaling in proneural clusters leads to multiple bristles Key Cell-Cell Signaling Pathways in Development TGF- /Activin/BMP Hedgehog Wnt Notch RTK/Ras/ERK JAK/STAT RTK pathways transduce signals by phosphorylation RTK/Ras/Erk pathways: A cascade of kinase activities leads to transcription factor activation Mutations in ras are responsible for a large proportion of human tumors Development of the C. elegans vulva (egg-laying apparatus) Vulval cell fates are specified by a combination of RTK/Ras/ERK and Notch signaling Key Cell-Cell Signaling Pathways in Development TGF- /Activin/BMP Hedgehog Wnt Notch RTK/Ras/ERK JAK/STAT Activation of the JAK/STAT pathway leads to dimerization and nuclear entry of Stat transcription factors Constitutive activation of the JAK/STAT pathway causes severe forms of dwarfism ...
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