Biology 624 - Developmental Genetics
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Biology 624 - Developmental Genetics. Lecture #6 - Tube Formation I. Tube Formation is critical to forming: Lung Kidney Mammary gland Blood vessels Fly trachea C. elegans excretory system (1 cell!). From Nelson, 2003. There are three types of tubes: Multicellular

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Biology 624 - Developmental Genetics

Lecture #6 - Tube Formation I


Tube Formation is critical to forming:

Lung

Kidney

Mammary gland

Blood vessels

Fly trachea

C. elegans excretory system (1 cell!)

From Nelson, 2003


There are three types of tubes:

Multicellular

Unicellular, with autocellular junction

Unicellular, seamless

From Lubarsky and Krasnow, 2003


Processes of Tubulogenesis

From Lubarsky and Krasnow, 2003


Processes of Tubulogenesis

From Lubarsky and Krasnow, 2003


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


MDCK in collagen starts with a

polarized cyst

Gp135 = apical, red

b-catenin = basolateral, green

From Pollack et al, 98; Zegers et al, 03


Upon addition of HGF, some cells

form an extension outward on their

basolateral side

E-cadherin,

basolateral

Gp135, apical

From Pollack et al, 98


The extended cell divides, and

cells in the extension express E-cadherin

but not gp135

E-cadherin,

basolateral

Gp135, apical

From Pollack et al, 98


As the lumen begins to reform in the

extension, gp135 is re-expressed

on the new apical surface

E-cadherin,

basolateral

Gp135, apical

From Pollack et al, 98

From Pollack et al, 98


As lumen formation continues, cells

re-establish basolateral expression of

E-cadherin

E-cadherin,

basolateral

Gp135, apical

From Pollack et al, 98


Model derived from this study:

Stimulation of migration is the first step in tubulogenesis

Apical/basal polarity is transiently lost and then restored

Discontinuous lumens form in tubules

Cell-cell contacts are retained throughout the process


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


Apical membrane biogenesis is important

For lumen formation in MDCK cells

From Lubarsky and Krasnow, 03




MDCK tubulogenesis can be divided into stages polarity

with different molecular requirements

Requires

ERK activation

Requires

MMP activity

From O’Brienet al, 04


MDCK tubulogenesis polarity

p-EMT requires ERK

activation

Nuclei=blue

Actin = red

From O’Brien et al, 04


MDCK tubulogenesis polarity

redifferentiation

Requires MMP activity

Nuclei=blue

Actin = red

From O’Brien et al, 04


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