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L11 Long Range Control: WNT Signalling
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L11 Long Range Control: WNT Signalling

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@TimeHonoredLimerick2759

Questions and Answers

What is the main function of WNT ligands?

  • Promoting apoptosis in cells
  • Regulating gene expression based on cell concentration (correct)
  • Transmitting signals through direct cell contact
  • Facilitating muscle contraction

    • WNT signalling pathways only operate through paracrine communication.

    False

    What protein does a WNT ligand bind to initiate the signalling pathway?

    frizzled (FZD) receptor

    WNT is a portmanteau created from the names __________ and __________.

    <p>Wingless, Int-1</p> Signup and view all the answers

    Match the following WNT-related terms with their definitions:

    <p>Frizzled (FZD) = The receptor that binds WNT ligands Dishevelled = A protein activated inside the cell by WNT binding Morphogen = A signaling molecule that induces different responses based on concentration Autocrine signalling = Cell communication where a cell signals to itself</p> Signup and view all the answers

    Which of the following is NOT a well-studied tissue involved in WNT signaling?

    <p>Cardiac tissue</p> Signup and view all the answers

    Only 10 WNT genes exist in mammals.

    <p>False</p> Signup and view all the answers

    Name one consequence of mutations in key steps of WNT signalling.

    <p>Developmental abnormalities or cancer</p> Signup and view all the answers

    What is the primary role of beta-catenin in the canonical Wnt signaling pathway?

    <p>Activates gene transcription</p> Signup and view all the answers

    Dishevelled is responsible for ubiquitinating beta-catenin.

    <p>False</p> Signup and view all the answers

    What proteins are part of the destruction complex that ubiquitinates beta-catenin?

    <p>GSK3 and Axin</p> Signup and view all the answers

    The target genes of TCF include _____ and _____, creating a negative feedback loop for Wnt signaling.

    <p>axin 2, lef1</p> Signup and view all the answers

    Which of the following events occurs first in the canonical Wnt signaling pathway?

    <p>Wnt binds to frizzled</p> Signup and view all the answers

    Match the following components of Wnt signaling with their functions:

    <p>Frizzled = Receptor for Wnt Porcupine = Responsible for palmitoylation of Wnt GSK3 = Part of the destruction complex TCF = Transcription factor activated by beta-catenin</p> Signup and view all the answers

    Palmitoylation and glycosylation are modifications that Wnt proteins undergo.

    <p>True</p> Signup and view all the answers

    What is the role of Porcupine in Wnt signaling?

    <p>It is responsible for palmitoylation and possibly ER transport and secretion of Wnt.</p> Signup and view all the answers

    What is the role of SOX2+ stem cells in the pituitary gland?

    <p>They secrete paracrine WNT ligands that promote proliferation.</p> Signup and view all the answers

    WNT signalling has the same effects in all cell types.

    <p>False</p> Signup and view all the answers

    What consequence is observed when there is Wls deletion in SOX2 stem cells?

    <p>Hypoplasia</p> Signup and view all the answers

    WNT signalling is required at all stages of __________ development for patterning, branching, and proliferation.

    <p>mammary gland</p> Signup and view all the answers

    Match the WNT-related concepts with their descriptions:

    <p>WNT signalling in cancer = Can lead to the formation of small tumors during tooth development Paracrine WNT ligands = Secreted by stem cells to promote neighboring cell proliferation WNT antagonists = Prevent WNT upregulation TCF3 absence = Results in no head formation during development</p> Signup and view all the answers

    How does WNT signalling impact embryonic development?

    <p>It serves as posteriorising signals.</p> Signup and view all the answers

    Which of the following proteins are considered WNT antagonists?

    <p>Dickkopf (Dkk)</p> Signup and view all the answers

    Wntless (Wls) is involved in WNT secretion and is restricted to particular cell types.

    <p>False</p> Signup and view all the answers

    Name one role of WNT in the cell cycle.

    <p>Inhibiting GSK3</p> Signup and view all the answers

    Wnt antagonists like WNT inhibitory factors (WIFs) bind to WNTs to stop their usual __________.

    <p>action</p> Signup and view all the answers

    Match the WNT components with their functions:

    <p>Frizzled related proteins = Reduce WNT availability RSpondin = Agonist that inhibits WNT antagonists APC and Dvl = Regulate spindle attachment during division ZNFR3 and RNF43 = Lead to WNT internalisation</p> Signup and view all the answers

    Which proteins are known to interact with WNTs?

    <p>19 WNTs and 10 FZDs</p> Signup and view all the answers

    The presence of many isoforms of WNTs means that WNT signalling can be disrupted by a mutation in a single WNT or receptor.

    <p>False</p> Signup and view all the answers

    What is the consequence of WNT signalling on microtubule assembly?

    <p>Promotes microtubule assembly by tau stabilization</p> Signup and view all the answers

    Study Notes

    Understanding WNT Signalling

    • WNT ligands are significant morphogens, influencing cell responses and pattern formation based on their concentration.
    • Core functions of WNT include self-renewal of stem cells, proliferation, differentiation, and tissue patterning.
    • Major tissues studied include neural, intestinal, and epidermal systems.

    WNT Pathway Mechanism

    • The term "Wnt" is derived from "Wingless" and "Int-1".
    • WNT pathways can use paracrine (nearby communication) or autocrine (same-cell communication) signaling.
    • There are 19 mammalian WNT genes and 10 human Frizzled (FZD) receptors.
    • WNT pathway activation occurs when a WNT ligand binds to a FZD receptor, initiating a cascade through dishevelled protein.

    Canonical WNT Pathway

    • In the canonical pathway, the WNT ligand prevents the degradation of β-catenin.
    • The destruction complex involves proteins like GSK3 and Axin, which tag β-catenin for degradation.
    • When β-catenin is stabilized, it translocates to the nucleus, displacing Groucho bound to TCF, and activates transcription factors.

    Gene Expression and Feedback Loop

    • TCF/LEF factors switch from repression to activation upon β-catenin binding.
    • Key target genes activated include Axin2 and Lef1, forming a negative feedback loop to regulate WNT signaling.

    Regulation of WNT Signaling

    • WNT processing can be modified through palmitoylation and glycosylation, mediated by the enzyme Porcupine.
    • Wntless/Wls/Evi proteins are essential for the secretion of WNT signals; their functions are not restricted to specific cell types.
    • WNT antagonists include Frizzled related proteins (FRPs), WNT inhibitory factors (WIFs), and Dickkopf (Dkk), which help modulate WNT activity.

    Biological Context of WNT Signaling

    • WNT plays critical roles in the cell cycle, specifically regulating G1 and S phase progression.
    • GSK3 inhibition by WNT paves the way for the activation of cyclins D and E.
    • Proper distribution of chromosomes during cell division requires GSK3, β-catenin, and Axin2 at the centrosome.

    Homeostasis and Stem Cell Interaction

    • WNT pathways promote proliferation in cells near SOX2+ stem cells by secreting paracrine WNT ligands.
    • Deletion of Wls in SOX2+ cells leads to hypoplasia, showcasing WNT’s role in differentiation and tissue maintenance.

    WNT Signaling and Cancer

    • Alterations in WNT signaling can lead to cancer, particularly through mutations or overexpression.
    • Activation via β-catenin stabilization during development can predispose to tumor formation.
    • Mutations affecting stem cell-secreted WNT signals can lead to tumor reformation.

    Developmental Importance of WNT

    • WNT signaling provides crucial posteriorising information during embryonic development to maintain anterior identity.
    • Factors that inhibit WNT upregulation are pivotal in preventing aberrant tissue formation.
    • Absence of repressive factors like TCF3 can lead to significant developmental consequences, such as failure in head formation.

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    Description

    This quiz explores the long-range control of gene expression through WNT signalling. Participants will delve into the molecular events necessary for transducing extracellular signals into changes in gene expression in the nucleus, alongside a review of internal regulatory processes. Gain a comprehensive understanding of how secreted signalling proteins influence gene regulation.

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