Cell-Cell Communication in DevelopmentBiology 4361 - Developmental Biology2009Cell-Cell CommunicationConceptsCells develop in the context of their environment, including: - their immediate cellular neighborhood- their tissue identity- their position in the body.Developing cells receive signals from each of these locations,and they, in turn, signal the cells around them.1) A signal2) A receptor for that signal3) A mechanism to translate and/or transport the signal 4) A mechanism to translate the signal to a stimulation(or repression) of gene expressionThe components of this signal/response system must include:Cell-Cell CommunicationJuxtacrine signaling / extracellular matrix signalingOverviewInduction and competence- how do cells and tissues “know” how to develop?Paracrine factors – a type of inducer molecule- inter- and intracellular signalsSignal transduction / signal transduction cascades- response to signals at the molecular levelMaintenance of the differentiated state- how to ensure that a tissue remains stableCell death pathwaysCross-talkInduction and CompetenceCompetence – the ability of a cell or tissue to respond to a specific inductive signal.Development depends on the precise arrangement of tissues and cells.- organ construction is precisely coordinated in time and space- arrangements of cells and tissues change over timeInduction – interaction at close range between two or more cells or tissues with different histories and properties.Inducer – tissue that produces a signal that changes cellular behaviorResponder – tissue being induced; the target tissueNote – the target tissue must be capable of responding =Induction - Vertebrate Eye DevelopmentMRC Human Embryo Bank / Wellcome Photo LibraryInduction - Vertebrate Eye DevelopmentThe developing lens then induces brain to form the optic cupLens placode (tissue thickening) induced in head ectoderm by close contact with neural (brain) tissueInduction and CompetencePax6Pax6Competence FactorsCompetence - ability of a cell or tissue to respondto a specific inductive signal- actively acquired (and can also be transient)During lens induction Pax6 is expressed in the head ectoderm, but not in other regions of surface ectodermPax6 is a competence factor for lens inductionInducersInducers are molecular components; e.g. optic vesicle inducers: - BMP4 (bone morphogenic protein 4)- induces Sox2 and Sox3 transcription factors- Fgf8 (fibroblast growth factor 8)- induces L-Maf transcription factorStepwise InductionInducersOften multiple inducer tissues operate on a structure; e.g. for frog lens:1stinducer - pharyngeal endoderm & heart-forming mesoderm2ndinducer - anterior neural plate (including signal for ectoderm Pax6 synthesis)Reciprocal InductionABCDMouse Lens – Reciprocal InductionInductive InteractionsInteractions between epithelia and mesenchyme:- mesenchyme plays an instructive role (as the inducing tissue) - initiates gene activity in epithelial cellsInstructive and Permissive InteractionsA signal from the inducing cell is necessary for initiating new gene expression in the responding cellGeneral principles of instructive interactions:1. In the presence of tissue A, responding tissue B develops in a certain way.2. In the absence of tissue A, responding tissue B does not develop in that way.3. In the absence of tissue A, but in the presence of tissue C, tissue B does not develop in that way.e.g. optic vesicle placed under a new region of head ectoderm-without the inducing cell, the responding cell is not capable of differentiating (in that particular way).Instructive interactions restrict the cell’s developmental optionsInstructive:Instructive and Permissive InteractionsPermissive:Permissive interactions tend to regulate the degree of expressionof the remaining developmental potential of the cell.The responding tissue has already been specified; needs only an environment that allows the expression of those traits.A signal from the inducing cell is necessary for initiating new gene expression in the responding cellInstructive:Epithelia and MesenchymeMany inductions involve interactions between epithelia and mesenchyme.Mesenchymal-epithelial interactions:Mesenchyme initiates gene activity in epithelial cellsMesenchyme – loosely packed, unconnected- derived from mesoderm or neural crestAll organs consist of an epithelium and an associated mesenchyme.Epithelia – sheets or tubes of connected cells- originate from any cell layerSkin Epithelium & MesenchymeEpitheliumMesenchymeinductivesignalsepithelial derivatives:- feathers- hair - mammary glands- scales - sweat glandsderivative type depends on restrictions by regionand geneticsRegional Specificity of InductionRegional Specificity - source of the mesenchyme (inducing tissue)determines the structure of the epithelial derivative.Genetic Specificity of InductionMesenchyme induces epithelial structures……but can only induce what the epithelium is genetically able to produceGenetic specificity – epithelial response is limited to genomic capabilityCell-Cell CommunicationJuxtacrine signaling / extracellular matrix signalingOverviewInduction and competence- how do cells and tissues “know” how to develop?Paracrine factors – a type of inducer molecule- inter- and intracellular signalsMaintenance of the differentiated state- how to ensure that a tissue remains stableSignal transduction / signal transduction cascades- response to signals at the molecular level- signaling pathways gone bad – proto-oncogenesCell death pathwaysCross-talkCell-Cell CommunicationConceptsCells develop in the context of their environment, including: - their immediate cellular neighborhood- their tissue identity- their position in the body.Developing cells receive signals from each of these locations,and they, in turn, signal the cells around them.1) A signal2) A receptor for that signal3) A mechanism to translate and/or transport the signal 4) A mechanism to translate the signal to a stimulation(or repression) of gene expressionThe components of this signal/response system must include:Inducing SignalsAlso:autocrine (self-generated) signalsendocrine signalsParacrine FactorsFibroblast growth factor (FGF)Hedgehog familyWingless family (Wnt)TGF-β superfamily (TGF = transforming growth factor)- TGF-β family- Activin family- Bone morphogenic proteins (BMPs)- Vg1 familySignaling molecules (proteins) produced by one cell (tissue) and distributed via diffusion to a localized