General idea and concepts of cell-cell signaling Cell signaling: Mechanisms that one cell uses to communicate with and influence the behavior of another cell. In a broader sense, the signaling could include environmental cues received by a cell such as smell, light, mechanic pressure, and heat etc. Three ways of cell signaling long-ranch signaling by secreted molecules contact signaling by plasma-membrane-bound molecules contact signaling via GAP junctions

Receptors: a. Enzymed-linked receptors -receptor protein kinases: tyrosine kinases, serine/thronine kinases - receptors coupled to protein kinases -protein tyrosine phosphatase receptors -ligand binding leads to activation of intrinsic enzyme activity, such as guanylyl cyclase catalytic domain b. G protein-linked seven transmembrane receptors c. Ion channel-linked receptors d. Intracellular Receptors--Steriod hormone receptors e. Receptors with death domain

Signal transduction pathways Wnt signaling pathway TGF beta signaling pathway Notch signaling pathway Small RNA signaling pathways cell death pathways - genetic pathways - biochemical pathways - death signaling pathways - radiation-induced bystander effect pathway - engulfment signaling pathways

Embryo development Mosaic Development (autonomous specification: determined by local determinants and no cell-cell interaction) Experimental test: remove one blastomere, the blastomere still develop as it will be in the original embryo Regulative Development (conditional specificaiton: determined by cell-cell interaction and local determinants not important; e.g. mouse) Experimental test: if remove one blastomere, the other blastomere will take over and the embryo is fine. Intermediate (Xenopus, fly and C. elegans)  

Experimental systems C. elegans Drosophila Mouse Human cultured cells

Approaches and techniques Genetic approaches   Genetic approaches Suppressor screen Enhancer screen Phenotypic screen Epistasis analyis Complementation tests Mosaic analysis Transformation rescue Sequencing of mutations Maternal effects

Biochemical approaches Co-IP hard-core protein purification mass spectrometry analysis Western blot analysis Enzymatic assays (kinases, proteases) Pulse chase experiments   Molecular Biological approaches Over-expression In vitro mutagenesis on DNA dsRNA injection Cell Biological approaches Cell or tissue isolation, mixing, and transplantation Micro-manipulation Immunostaining GFP fusion labeling LacZ staining Electron microscopy (EM) and tomography

Advantage or disadvantage of various approaches Genetic approach Help systematically identify the important components in a particular biological process Help determine the genetic relationships among different genes in the same pathway. But genetics often can not reveal the mechanisms underlying the biological process.   Biochemical approaches Very effective in elucidating the detailed mechanisms underlying a biological process. Can also help identify components of a biological process but usually can not reveal the whole picture and is restricted by the availability and relative quantity of materials, the experimental techniques or methods.

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