Cell-cell Communications in Development

Induction and Competence What do we mean by induction? How do we define competence? Where does Pax6 fit in? Induction – influence of one group of cells on adjacent cells Competence – able to respond to inducer Pax6 is a competence factor – needed by responder

Induction and Competence Where can we observe reciprocal inductions? Formation of eye in mouse

Induction and Competence What is the difference between instructive and permissive interactions? Instructive – inducing cell provides needed information to responder Permissive –all information is present in responder, requires a favorable environment

Epithelial-mesenchymal interactions Nature of epidermal structure depends upon from where mesenchyme comes How does this diagram illustrate the regional specificity of induction?

Epithelial-mesenchymal interactions Responder’s genome dictates structures that will form How does this experiment illustrate the genetic specificity of induction?

Paracrine Factors in Development What is the connection between paracrine factors and induction?

Paracrine Factors in Development How do fibroblast growth factors (FGF’s) induce changes in cells? Leads to phosphorylation and activation of cell protein About 24 different genes producing FGF’s are known

Paracrine Factors in Development What is the Hedgehog family? Family of genes acting as paracrine factors – induce particular tissues or tissue boundaries In vertebrates, sonic hedgehog, desert hedgehog, indian hedgehog Picture show active sonic hedgehog gene

Paracrine Factors in Development The wnt family? Family of proteins involved in induction of urogenital development among other things

Paracrine Factors in Development The TGF-β superfamily? BMP’s within TGF are involved in inducing bone formation; TGF are involved in formation of extracellular matrix and in regulating cell division

Signal Transduction Pathways What is involved in signal transduction? Transmembrane protein; extracellular receptor binds ligand; induces conformational change in receptor; changes cyctoplasmic domain; activates enzyme; alters intracellular protein

Signal Transduction Pathways How does the RTK pathway promote cell-cell induction? Leads to activation of trascription factor in nucleus

Signal Transduction Pathways What are examples of some specific inductions that use the RTK pathway? Induction of photoreceptors in Drosophilia Induction of vulva in C. elegans Induction of melanin forming pathway in pigment cells of retinia; related to activation of Mitf transcription factor

Signal Transduction Pathways How does the Smad pathway compare with the RTK pathway? Different ligands; heterodimeric receptor; autophosphorylation;phosphorylated intermediates; activation of transcription factors

Signal Transduction Pathways What pathway mediates both the differentiation of blood cells and the formation of milk for lactation? JAK-STAT; also important in human fetal bone growth

Signal Transduction Pathways How can the Wnt pathway mediate cell division? What are the ramifications of this pathway? B-catenin causes activation of cell division genes such as c-myc

Signal Transduction Pathways How does the sonic hedgehog paracrine factor influence limb and neural development in vertebrates? Mutants of sonic hedgehog can lead to limb abnormalities and single eye formations

Signal Transduction Pathways What happens in the absence of sonic hedgehog? How is cholesterol involved here?

Cell Death Pathways What is the difference between apoptosis and necrosis? Why is apoptosis critical for development? What initiates apoptosis? apoptosis – programmed cell death; necrosis – cell death due to disease or infection needed for digit formation, spacing of neurons, generating middle ear, etc. signal molecules like BMP4 in teeth

Cell Death Pathways What role has C. elegans played in our knowledge of apoptosis? Brenner, Horvitz, Sulston – Nobel prize in 2002 CED-9 can bind to and inactivate CED-4 CED-4 protease activating factor; CED-3 protease in mammals – proteases caspase 9 and 3 are similar to CED-3 and Apaf1 is homologue of CED-4 and Bcl2 is similar to CED-9

Juxtacrine Signaling How is this type of signaling different from paracrine signaling? signal molecule is a protein that resides in adjacent cell member generally doesn’t involve a diffusable signal molecule

Juxtacrine Signaling Notch proteins are important receptors in neuron development

Juxtacrine Signaling Ligand resides in extracellular matrix of signaling cell fibronectin laminin What kinds of receptors are involved? integrins – bind to arginine-glycine-aspartate extracellularly and intracellularly bind to α-actinin and talin matrix has been shown to induce specific gene expression in liver, testis and mammary gland

Juxtacrine Signaling Gene activation by matrix attachment

Juxtacrine Signaling signal transmitted from cytoplasm of one cell directly to cytoplasm of second cell use gap junction antibodies to connexins cause vary forms of abnormal development

Pathway’s Cross Talk transcription may require activation of two pathways one receptor can activate different pathways differentiation of T lymphocyte FGF can activate RTK or STAT pathwys

Maintaining Differentiation Transcription factor as its own enhancer MyoD factor in muscle cells

Maintaining Differentiation Prevent nucleosome formation

Maintaining Differentiation Autocrine stimulation Sertoli cells of testis

Maintaining Differentiation Paracrine loop vertebrate limb