BIOL 4330 1st Edition Lecture 3 Outline of Last Lecture I. Developmental GeneticsII. Gene Regulation in DevelopmentIII. Differential Gene Expressiona. Methylationb. nRNA SplicingRNA Processing Outline of Current Lecture I. Morphogenesisa. Three Mechanisms of Cell-Cell CommunicationII. Epithelial Mesenchymal InteractionsIII. Paracrine FactorsIV. Maintaining the Differentiated StateCurrent LectureMorphogenesis is the formation of organized animal bodies.Key questions:1) How are separate tissues formed from population of cells?2) How are organs constructed from tissues?3) How do organs form in particular locations, and how do migrating cells reach their destinations?4) How do organs and their cells grow, and how is their growth coordinated throughout development?5) How do organs achieve polarity?Three Mechanisms of cell-cell communication- Cell Adhesion- Cell Migration- Cell SignalingCell Adhesion – Differential Cell AffinityThese notes represent a detailed interpretation of the professor’s lecture. GradeBuddy is best used as a supplement to your own notes, not as a substitute.Cell surface properties: reaggregation of cells from amphibian neurulae (after neural tube formation) in no case do the recombined cells remain randomly mixed – one tissue types completely envelops the otherSelective affinity – sorting out and reconstruction of spatial relationships in aggregates of embryonic amphibian cells. Final positions of the reaggregated cells reflect their respective positions in the embryo. Cells do not sort randomly.Cadherins = calcium-dependant adhesion molecules. They are transmembrane proteins that interact with other cadherins on adjacent cells. Anchored by catenins.Cadherin-catenin complex hold epithelial cells together.Cadherin-catenin complex bind to actin (microfilament) cytoskeleton.The importance of cadherins for maintaining cohesion between developing cells can be demonstrated by interfering with their production.Disrupted oocyte with antisense against cadherin mRNA cannot make cadherin so disperse when animal cap is removed. When a frog gastrula is injected with non functioning N-cadherin gene on one side, the epidermis and neural tissue can fail to separate.Cell migration is common in both epithelial and mesenchymal cells.1) Polarization – reorganization of cells and identification of the cell’s front and back causedby diffusing signals (chemotactic protein) or extracellular matrix signals.In epithelial cells, the motive force is provided by the edge of the sheet and the others follow passively.In mesenchymal cells, individual cells become polarized and migrate through the extracellular matrix.2) Protrusion of the leading edge – mechanical force for this is the polymerization of the actin microfilaments at the cell membrane, forming long parallel bundles (filopodia) or broad sheets (lamellipodia)3) Adhesion of the cell to its extracellular substrate – moving cell needs something to push on & attaches to the surrounding matrixKey molecules are integrin proteins, which span the cell membrane, connecting the extracellular matrix outside the cell to the actin cytoskeleton inside the cell and form focal adhesion sites.4) Release of adhesions in the rear allowing the cell to migrate forward-stretch-sensitive Ca2+ channels are opened and that the released Ca2+ ions activate proteases that destroy the focal adhesion sites.In cell signaling, induction and competence is key to how organs form.Inductive interaction is made up of two components:- Inducer: the tissue that produces the signal or signals that changes the cellular behavior of the other tissue (often a paracrine factor)Paracrine factors are proteins made by the cell or a group of cells that alter the behavior or differentiation of adjacent cells This kind of interaction at close range between two or more cells or tissues of different histories and properties is called induction.- Responder: the tissue being induced must have both a receptor protein for the inducing factor and the ability to respond to the signal. The ability to respond to a specific inductive signal is called competence.Signal Transmission from Environment to Genome through Direct Induction When one tissue induces the differentiation of another during normal embryonic development (i.e. when presumptive neural retina tells the outer ectoderm to become the lens of the eye) soluble factors are sent from the inducing tissue are received by receptors in the adjacent tissue.Epithelial Mesenchymal InteractionsBest cases of induction are those involving the interactions of sheets of epithelial cells with adjacent mesenchymal cells. Epithelia – are sheets or tubes of connected cells: they can originate from any germ layer Mesenchyme - are loosely packed, unconnected cells, derived from mesoderm or neural crest. All organs consist of epithelium and associated mesenchyme, so these epithelial - mesenchymal interactions are one of the most important phenomenon in nature.Properties of epithelial-mesenchymal interactions1) Regional specification of induction – epithelial cells signal underlying mesenchymal cells to secrete proteins which in turn trigger the epithelial cells to respond by forming regional specific structures.2) Genetic specifity of induction – mesenchymal cells may instruct the epithelial cells as to what genes to activate and the responding epithelium may complyParacrine Factors: The Inducer (signaling) molecules Induction of numerous organs is effected by a small set of paracrine factors or growth and differentiationfactors that diffuse over small distances. The embryo has a small “toolkit” to construct most of the organs. Paracrine factors function by binding to a receptor that initiates a series of enzymatic reactions within the cell. These enzymatic reactions have an end point that is either regulation of transcription factors (such that different genes are expressed) or the regulation of the cytoskeleton (such that cells responding to the factors alter their shape or migrate). Pathways of responses to the paracrine factors o[en have several end points and are called signal transduction cascades. Signal Transduction Cascades – The response to inducersFour major families of paracrine factors based on their structure:1) Fibroblast growth factor (FGF) family & RTK pathway2) Hedgehog families (Indian, Desert, Sonic)3) The Wingless, or Wnt family – cysteine rich glycoproteins4) TGF-beta