Term
| Which types of cytoskeletal filaments are most important for the "protrusive" activity of cells? How is this process achieved? |
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Definition
Actin-based microfilaments
Filopodia and Lamellopodia are formed when Arp complexes nucleate the actin meshwork, with Rac promoting their formation and Rho promoting their retraction.
Cells attach to other cells and the ECM, and exert traction forces via Myosin II, |
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Term
| How do Cadherins regulate cell division in many cells? |
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Definition
Cadherins hold cells together, preventing their lateral diffusion and division.
When Cadherin-links are broken, cells tend to divide. |
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Term
| Explain how neutrophils and neuronal axons exhibit chemotaxis. |
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Definition
1) Neutrophils send concentration gradients of 1% difference in formylated peptides expressed by bacteria (they go to the bacteria and engulf them!)
2) Axons are attracted to soluble netrin proteins that are secreted by intermediate targets. |
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Term
| What is the difference b/w heterophillic and homophillic binding? Provide some examples. |
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Definition
1) Heterophillic involves two different receptors (integrins to laminin and fibronectin, Eph-receptor to ephrins, Immunoglobulins can be either)
2) Homophillic involves two of the same molecule (Cadherins, Immunoglobulin N-CAM) |
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Term
| How do ephrins regulate neuronal growth paths? What about integrins and immunoglobulins? |
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Definition
RTK EPH receptors bind ephrins as ligands and act as (-) cues for neuronal growth cones.
Additionally, integrins and immunoglobulins act as (+) cues. |
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Term
| How do fibroblasts modify their local environments to promote movement? |
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Definition
| Secrete fibronectin and express integrins that can bind firbronectin (laying down the road they will walk) |
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Term
| How are serine and metalloproteinases involved in cellular locomotion? |
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Definition
| Cells secrete these proteinases to digest away paths in the ECM for them to pass through. Tissue inhibitors of these molecules such as serpins (serine) and TIMPs (metalloproteinases) limit this proteolysis and cellular movement. |
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Term
| What particular structures emerge from Cranial, Cranial + spinal, and Spinal neural crest cell populations? |
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Definition
1) Cranial- Connective tissue around eye, cranial nerve ganglia, pharyngeal arch cartilage.
2) Cranial + spinal- melanocytes of skin, enteric ganglia, glial cells in PNS (Schwann)
3) Spinal- preaortic ganglia, DRG, adrenal medulla |
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Term
| Provide a molecular explanation for how neural crest cells migrate from the neural tube to neighboring cells. |
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Definition
In neural tube, they express N-CAM and N-Cadherin to integrate into the neural epithelium.
In preparation for migration, they stop expressing these and begin to express tissue specific integrins. When they reach their targets, enviornmental growth factors such as BDNF, bFGF and GCs promote differention. |
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Term
| A patient presents with an absent Auerbach's plexus. What disease are they likely to have and how does it arise? |
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Definition
Hirschsprung's (no innervation or mobility of descending colon)
Mutation in RET receptor (binds GDNF) inhibits neural crest migration to bowel. |
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Term
| Explain how stem cell migration occurs in the gut. |
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Definition
| Stem cells generate absorptive, brush-border cells, goblet cells, and enteroendocrine cells which travel as SHEETS (not individual cells) to cover the villi |
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Term
| How do lymphocytes respond to inflammatory cues? |
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Definition
Endothelial cell venules express carb-binding, calcium-sensitive Selectins which bind carbs on lymphocytes.
After lymphocytes reach their target, they are slowed, and they stably attach and move through venules in the endothelial wall via integrins.
They then migrate to inflammatory tissue via chemotaxis. |
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Term
| Describe the progressive development of melanomas. What does it have to do with keratinocytes? |
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Definition
1) UV-exposure initiates radial growth
2) Vertical growth associated with changes in cell surface integrins and cadherins leads to metastatic spread.
3) Keratinocytes usually sterically prevent spread (5:1 ratio), but they are overcome following malignant transformation.
** E-cadherin expression in melanoma cells using AAVs reduce tumorigenicity in vivo, and restores keratinocyte-dependent normal melanocytic phenotype in culture. ** |
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