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28 Cards in this Set
- Front
- Back
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What are the major signalling pathways used during development? |
- Notch - Wnt - Hedgehog - TGF-b (TGFb, BMP, Nodal) - RTK family (FGF, EGF) |
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How is gene expression regulated? |
- Extracellular signals regulate transcription factors which regulate gene expression |
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- How many signalling pathways are there? |
- relatively few - the same signalling pathway can be responsible for multiple developmental processes |
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Are signalling pathways very different in different species? |
- no, signalling pathways are well conserved evolutionary - the same pathways are found looking at the same process in different organisms |
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What are the two types of receptors of extracellular signals? |
- Cell-surface receptors - Notch, Wnt, Hedgehog, TGFb, RTK - Intracellular receptors - Retanoic acid - RA |
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How do small signalling pathways generate huge diversity of cells and patterns? |
- Gene duplication - OR the response of cells depends on other signals the cells is receiving simultaneously - Cells have different histories |
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How does gene duplication contribute to the diversity of the signalling pathways? |
- the basic components of a pathway are often encoded by small families of closely related genes |
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How do cells have different "histories"? |
- the selection of transcription factors and other proteins and RNAs it contains and the state of its chromatin will respond differently |
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Give an exam of cell "history"? |
- transplant embryonic ear region into trunk region of amphibian embryo and you get extra limbs - this is because the developing ear is a source of FGF and early limb development requires FGF - the same signal is interpreted in different ways by cells in different states |
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How does the Notch signalling pathway work? |
- Notch is a receptor, working with ligands such as Delta or Serrate; - A proteolytic fragment (intracellular domain of Notch receptor) is translocated to the nucleus |
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Give an example of a target transcription factor of Notch: |
- RBP, Su-H (drosophila), sometimes called CSL family |
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What are the roles of Notch? |
- responsible for cell fate, lateral inhibition, asymmetric cell division |
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What are the essentials for Notch signalling? |
- it is contact dependent - signalling cell and target cell must bind their appropriate membrane-bound signal molecules |
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Give an example of Notch signalling?- |
- Lateral inhibition (mediated by Delta as well) e.g. neural development - first there is a group of unspecified epithelial cells - surrounding cells bind to the middle cell - it differentiates into a neural cell |
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What are the basic mechanisms of the Wnt signalling pathway? |
- The receptor Wnt is the Frizzled family; - regulation is through protein interactions and GSK3 kinase - Wnt prevents degradation of cytoplasmic transcription factor |
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What is the target transcription factor of Wnt? |
- b-catenin, TCF |
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What are the roles of Wnt? |
- D/V axis in Xenopus - limb development - Drosophila segmentation - Proliferation of stem cells |
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Describe how the Wnt signalling pathway works: |
- Wnt is an extracellular molecule, binding to Frizzle, which is integrated in the membrane - When Wnt binds, Frizzled locks Dishevelled and other components into place - Dishevelled normally keeps other components from degrading b-catening |
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What is the basic mechanism of the Hedgehog pathway? |
- Patched is the receptor - membrane bound - When Hh is not binding Patched reactions happen that cleave Ci/Gli - represses transcription; - when Hh binds - it prevents cleavage of the target transcription factor |
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What are the target transcription factors of Hedgehog? |
- Gli/Ci |
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What is the basic mechanism of TGF-b signalling? |
- phosphorylation of cytoplasmic transcription factor and translocation to nucleus |
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What is the target transcription factor of TGF-b? |
- SMAD |
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How does the TGF-b function? |
- Receptors dimerise - Ser/Thr phosphorylation of SMAD takes place in the cytoplasm - |
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What is the role of TGF-b? |
- mesoderm induction and patterning (which is concentration dependent) |
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What is the basic mechanism of RTK signalling? |
- It forms a phosphorylation cascade to activate the transcription factor in the nucleus |
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What are RTK's (Receptor tyrosine kinase) transcription factors? |
It has many... |
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How does RTK function? |
- a signal binds to the RTK, which stimulates Ras-Mapk cascade, which ends by phosphorylating a nuclear transcription factor |
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What are the roles of RTK? |
- FGF - maintenance of mesoderm, limb bud signal from apical ridge, lung branching - EGF - cell proliferation, limb patterning |
