MDCK tubulogenesis can be divided into stages with different molecular requirements
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Transcript of MDCK tubulogenesis can be divided into stages with different molecular requirements
MDCK tubulogenesis can be divided into stageswith different molecular requirements
RequiresERK activation
RequiresMMP activity
From O’Brienet al, 04
MDCK tubulogenesis p-EMT requires ERKactivation
Nuclei=blueActin = red From O’Brien et al, 04
MDCK tubulogenesis redifferentiation Requires MMP activity
Nuclei=blueActin = red
From O’Brien et al, 04
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
Trachea Formation in Drosophila
MDCK in collagen forms a polarized cyst - how?
Gp135 = apical, redb-catenin = basolateral, green
From Zegers et al, 03
From Zegers et al, 03
Drive for three surfaces model - epithelial cells try to establish apical, lateral, and basal domains
+dnRAC
From Zegers et al, 03
MDCK cyst formation requires Racfor proper orientation of polarity
+dnRAC+Laminin
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
Steps in Tracheal Branching Morphogenesis
Ghabrial A, Krasnow M
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
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
Dysfusion is Required for Fusion Process
btl-gal4, UAS-actin-GFP btl-gal4, UAS-actin-GFP ; dys
Wild-type dys mutant
Dysfusion Regulates Downstream Targets with Various Functions
• Shotgun and CG13196 (cell adhesion)↑• members only (protein trafficking) ↑• CG15252 (unknown function) ↑• Trachealess (tracheal migration) ↓