mdck tubulogenesis can be divided into stages with different molecular requirements requires erk...
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![Page 1: MDCK tubulogenesis can be divided into stages with different molecular requirements Requires ERK activation Requires MMP activity From O’Brienet al,](https://reader036.vdocuments.us/reader036/viewer/2022062407/56649d7f5503460f94a631aa/html5/thumbnails/1.jpg)
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![Page 3: MDCK tubulogenesis can be divided into stages with different molecular requirements Requires ERK activation Requires MMP activity From O’Brienet al,](https://reader036.vdocuments.us/reader036/viewer/2022062407/56649d7f5503460f94a631aa/html5/thumbnails/3.jpg)
MDCK tubulogenesis can be divided into stageswith different molecular requirements
RequiresERK activation
RequiresMMP activity
From O’Brienet al, 04
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MDCK tubulogenesis p-EMT requires ERKactivation
Nuclei=blueActin = red From O’Brien et al, 04
![Page 5: MDCK tubulogenesis can be divided into stages with different molecular requirements Requires ERK activation Requires MMP activity From O’Brienet al,](https://reader036.vdocuments.us/reader036/viewer/2022062407/56649d7f5503460f94a631aa/html5/thumbnails/5.jpg)
MDCK tubulogenesis redifferentiation Requires MMP activity
Nuclei=blueActin = red
From O’Brien et al, 04
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Cellular Processes involved in Tube Formation
1. Cell-cell adhesion
2. Cell migration
3. Cell shape changes
4. Lumen formation
5. Cell division
6. Cell death
![Page 7: MDCK tubulogenesis can be divided into stages with different molecular requirements Requires ERK activation Requires MMP activity From O’Brienet al,](https://reader036.vdocuments.us/reader036/viewer/2022062407/56649d7f5503460f94a631aa/html5/thumbnails/7.jpg)
Trachea Formation in Drosophila
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MDCK in collagen forms a polarized cyst - how?
Gp135 = apical, redb-catenin = basolateral, green
From Zegers et al, 03
![Page 9: MDCK tubulogenesis can be divided into stages with different molecular requirements Requires ERK activation Requires MMP activity From O’Brienet al,](https://reader036.vdocuments.us/reader036/viewer/2022062407/56649d7f5503460f94a631aa/html5/thumbnails/9.jpg)
From Zegers et al, 03
Drive for three surfaces model - epithelial cells try to establish apical, lateral, and basal domains
![Page 10: MDCK tubulogenesis can be divided into stages with different molecular requirements Requires ERK activation Requires MMP activity From O’Brienet al,](https://reader036.vdocuments.us/reader036/viewer/2022062407/56649d7f5503460f94a631aa/html5/thumbnails/10.jpg)
+dnRAC
From Zegers et al, 03
MDCK cyst formation requires Racfor proper orientation of polarity
+dnRAC+Laminin
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Differential Regulation of Junctional ProteinsDuring Tubulogenesis (same paper)
1. Adherens junctions (E-cadherin) move around, and new ones are made
2. ZO-1, a tight junction protein, is between apical and basolateral domains, and during extension is at cell-cell contact points
3. Desmosome components dpI/II are in large intracellular pools during tubulogenesis
![Page 12: MDCK tubulogenesis can be divided into stages with different molecular requirements Requires ERK activation Requires MMP activity From O’Brienet al,](https://reader036.vdocuments.us/reader036/viewer/2022062407/56649d7f5503460f94a631aa/html5/thumbnails/12.jpg)
Steps in Tracheal Branching Morphogenesis
Ghabrial A, Krasnow M
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Model of the FGF signaling Pathway in the Control of Cell Migration in Drosophila.
Bnl: BranchlessBtl: BreathlessDof: Downstream of FGF, StumpsCsw: Corkscrew(phosphatase)HSPG: heparan sulfate proteoglycan
Petit V, Affolter M
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Steps of Tracheal Tube Formation
• Tracheal sac formation Specification of tracheal cells (tracheal placodes) Invagination of the tracheal placode
• General branch outgrowth via FGF signaling• Branch-specific outgrowth is controlled by regional signals and branch
identity genes Branch identity dentermination DB migration requires Dpp signaling GB migration requires slit-robo signaling Tube elongation through cell intercalation
• Determination and differentiation of distinct cell types (fusion cell, terminal cell) Fusion process Terminal branching
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Dysfusion is Required for Fusion Process
btl-gal4, UAS-actin-GFP btl-gal4, UAS-actin-GFP ; dys
Wild-type dys mutant
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Dysfusion Regulates Downstream Targets with Various Functions
• Shotgun and CG13196 (cell adhesion)↑• members only (protein trafficking) ↑• CG15252 (unknown function) ↑• Trachealess (tracheal migration) ↓