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MDCK tubulogenesis can be divided into stages with different molecular requirements . Requires ERK activation. Requires MMP activity. From O’Brienet al, 04. MDCK tubulogenesis p-EMT requires ERK activation. Nuclei=blue Actin = red. From O’Brien et al, 04. MDCK tubulogenesis
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MDCK tubulogenesis can be divided into stages with different molecular requirements Requires ERK activation Requires MMP activity From O’Brienet al, 04
MDCK tubulogenesis p-EMT requires ERK activation Nuclei=blue Actin = red From O’Brien et al, 04
MDCK tubulogenesis redifferentiation Requires MMP activity Nuclei=blue Actin = red From O’Brien et al, 04
Cellular Processes involved in Tube Formation Cell-cell adhesion Cell migration Cell shape changes Lumen formation Cell division Cell death
MDCK in collagen forms a polarized cyst - how? Gp135 = apical, red b-catenin = basolateral, green From Zegers et al, 03
Drive for three surfaces model - epithelial cells try to establish apical, lateral, and basal domains From Zegers et al, 03
MDCK cyst formation requires Rac for proper orientation of polarity +dnRAC +dnRAC +Laminin From Zegers et al, 03
Differential Regulation of Junctional Proteins During Tubulogenesis (same paper) Adherens junctions (E-cadherin) move around, and new ones are made ZO-1, a tight junction protein, is between apical and basolateral domains, and during extension is at cell-cell contact points 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: Branchless Btl: Breathless Dof: Downstream of FGF, Stumps Csw: 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 Wild-type dys mutant btl-gal4, UAS-actin-GFP btl-gal4, UAS-actin-GFP ; dys
Dysfusion Regulates Downstream Targets with Various Functions • Shotgun and CG13196 (cell adhesion)↑ • members only (protein trafficking) ↑ • CG15252 (unknown function) ↑ • Trachealess (tracheal migration) ↓