CellCell Communication in Development Biology 4361  Developmental Biology June 25, 2008CellCell Communication Concepts Developing cells receive signals from each of these locations, and they, in turn, signal the cells around them. The components of this signal/response system must include: 1) a signal 2) a receptor for that signal 3) a mechanism to translate and/or transport the signal (or signal product) 4) a mechanism to translate the signal to a stimulation (or repression) of gene expression Cells in developing organisms develop in the context of their environment, including their immediate cellular neighborhood, their tissue identity, and their position in the body.CellCell Communication Cell death pathways Juxtacrine signaling / extracellular matrix signaling Overview Induction and competence How do cells and tissues “know” how to develop? Paracrine factors – a type of inducer molecule Inter and intracellular signals Signal transduction / signal transduction cascades Response to signals at the molecular level Maintenance of the differentiated state How to ensure that a tissue remains stable CrosstalkInduction and Competence Competence – 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 time Induction – 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 behavior Responder – tissue being induced; the target tissue.  Note  target tissue must be capable of responding =Induction  Vertebrate Eye Development Lens placode (tissue thickening) induced in head ectoderm by close contact with neural (brain) tissue The developing lens then induces brain to form the optic cupInduction and CompetencePax6 Pax6 Competence Factors Competence – the ability of a cell or tissue to respond to 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 ectoderm Pax6 is a competence factor for lens inductionInducers Inducers are molecular components; e.g. optic vesicle inducers:  BMP4 (bone morphogenic protein 4)  Fgf8 (fibroblast growth factor 8)  induces Sox2 and Sox3 transcription factors  induces LMaf transcription factorStepwise Induction Inducers Often multiple inducer tissues operate on a structure; e.g. for frog lens:  1 st inducer  pharyngeal endoderm & heartforming mesoderm  2 nd inducer  anterior neural plate (including signal for ectoderm Pax6 synthesis)Reciprocal Induction A B C DMouse Lens – Reciprocal InductionInductive Inter actions Many inductions involve interactions between epithelia and mesenchyme. Mesenchyme plays an instructive role (as the inducing tissue) – initiates gene activity in epithelial cellsInstructive and Permissive Interactions A signal from the inducing cell is necessary for initiating new gene expression in the responding cell General 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. Permissive: 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 tend to restrict the cell’s developmental options Instructive:  tend to regulate the degree of expression of 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.Epithelia and Mesenchyme Many inductions involve interactions between epithelia and mesenchyme. Mesenchymalepithelial interactions: Mesenchyme initiates gene activity in epithelial cells Mesenchyme – loosely packed, unconnected cells  derived from mesoderm or neural crest All organs consist of an epithelium and an associated mesenchyme. Epithelia – sheets or tubes of connected cells  originate from any cell layerSkin Epithelium & Mesenchyme Epithelium Mesenchyme inductive signals epithelial derivatives:  feathers  hair  mammary glands  scales  sweat glands derivative type depends on restrictions by region and geneticsRegional Specificity of Induction Regional Specificity  source of the mesenchyme (inducing tissue) determines the structure of the epithelial derivative.Genetic Specificity of Induction Mesenchyme induces epithelial structures   but can only induce what the epithelium is genetically able to produce Genetic specificity – epithelial response is limited to genomic capabilityCellCell Communication Cell death pathways Juxtacrine signaling/extracellular matrix signaling Overview Induction and competence How do cells and tissues “know” how to develop? Paracrine factors – inducer molecules Intracellular signals Maintenance of the differentiated state How to ensure that a tissue remains stable Crosstalk Signal transduction / signal transduction cascades Responses to inter and intracellular signaling Signaling pathways gone bad – ProtooncogenesCellCell Communication Concepts Developing cells receive signals from each of these locations, and they, in turn, signal the cells around them. The components of this signal/response system must include: 1) a signal 2) a receptor for that signal 3) a mechanism to translate and/or transport the signal (or signal product) 4) a mechanism to translate the signal to a stimulation (or repression) of gene expression Cells in developing organisms develop in the context of their environment, including their immediate cellular neighborhood, their tissue identity, and their position in the body.Inducing Signals Also: autocrine (selfgenerated) signals endocrine signalsParacrine Factors Fibroblast growth factor (FGF) Hedgehog family Wingless family (Wnt) TGFβ superfamily (TGF = transforming growth factor)  TGFβ family  Activin family  Bone morphogenic proteins (BMPs)  Vg1 family Signaling molecules (proteins)