mdck tubulogenesis can be divided into stages with different molecular requirements requires erk...

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) ↓