Figure 4. Cell shape-dependent switching between cell fates on microfabricated ECM islands.  Excerpted from "Mechanical control of tissue morphogenesis during embryological development".
Photo courtesy of  "Cytoskeleton: Making the cap fit" by Sarah Greaves.  

Cell membranes and Extracellular Matrix (ECM)

Morphogenesis. Image courtesy of artist Rick Companje
Figure 8. Nuclear Localization of Armadillo in Stomodeal-Primordium Cells during the First Phase of the Germ-Band Extension.  Excerpted from "Mechanical induction of Twist in the Drosophila Foregut/Stomodeal Primordium.
Figure 1. Planar Polarity in Epithelia. Excerpted from "Planar polarity and tissue morphogenesis"


 

Anna Means , Ph.D. (Organizer and Instructor )
Assistant Professor - Surgery and Cell and Developmental Biology 

Ela Knapik, M.D. (Organizer and Instructor) 
Associate Professor - Medicine and Cell and Developmental Biology

(For more information about CBIO341 please contact the Course Coordinator)

 

This module examines the interactions between cells and extracellular matrix (ECM) in the regulation of tissue and organ morphogenesis. While the bulk of developmental biology has focused more on transcriptional and signaling molecules that regulate specification and differentiation, there is a burgeoning field of study indicating the importance of the cellular microenvironment in the morphogenetic development of many tissues/organs. Specifically, there is increasing evidence that interactions of cells with ECM molecules regulate many structural aspects of development. We will explore the ways in which ECM/integrin interactions regulate the migration and coalescence of mesenchymal cells and the molding of epithelial sheets/tubes. We will also explore how these interactions are regulated at the level of protein modification and secretion of ECM molecules.

There are two books for this course that are highly recommended:  Principles of Development by Lewis Wolpert, and Developmental Biology by Scott F. Gilbert.  Copies of both books can be borrowed from the PDB Library.

Click on the appropriate module name for class specifics by date.

Class Date
Topics, Presentations & Readings
3/20/08 Introduction: Extracellular matrix (ECM) as a mechanical regulator of cell movement and tissue shapes   
    Cell-cell versus cell-ecm interactions
   
  • Focal adhesions
  • Cell-cell junctions
    Cell shape changes
    Making ECM more or less flexible
    Directional migration on ECM
    How is ECM locally altered and by whom?
  Required Readings
    Mechanical control of tissue morphogenesis during embryological development.
 2006 International Journal of Developmental Biology 50: 255-266
    Mechanical control of cyclic AMP signaling and gene transcription through integrins. 
2000 Nature Cell Biology 2: 666-668
  Optional Reading
    Mechanical induction of Twist in the Drosophila Foregut/Stomodeal Primordium.
2003 Current Biology 13: 1365-1377
  Assignment (Due 3/20/08)
  Prepare to discuss:
 
1.
 How do changes in cell shape affect tissue shape?
 
2.
 How can the ECM regulate cell shape change?
 
3.
 When making epithelial structures, how do ECM changes, proliferation, and cell shape changes need to interact? How could failure in any one of those 3 processes prevent tissue morphogenesis?
3/25/08 Role of ECM in epithelial migration
    Movement of cells within a sheet - Convergent extension
    Movement of epithelial sheets
    Gastrulation involution
    Drosophila endoderm migration
  Required Readings 
    Integrin a5b1 and Fibronectin Regulate Polarized Cell Protrusions Required for Xenopus Convergence and Extension.
2007 Current Biology 16: 833-844
    Morphogenesis in the absence of integrins: mutation of both Drosophila b subunits prevents midgut migration.
2004 Development 131: 5405-5415
  Assignment (Due 3/25/08)
    You have each been assigned figures from one of the readings listed above.  Please click on the 3/25/08 'assignment' to download your assignments and the instructions.  Please come to class prepared to discuss your findings.
3/27/08 Branching Morphogenesis
    Tubulogenesis: multiple mechanisms for shape change
    Role of MMPs in lung branching
    ECM stabilization in salivary gland branching
  Required Readings
    From fate to function: the Drosophila trachea and salivary gland as models for tubulogenesis.  2006 Differentiation 74: 326-348
    Ribbon encodes a novel BTB/POZ protein required for directed cell migration in Drosophila melanogaster.  2001 Development 128: 3001-3015
  Assignment (Due 3/27/08)
4/1/08 ECM Synthesis and export during embryonic development - Part I (Ela Knapik)
  Background Readings  
    Assembly, organization, and function of he COPII coat.  2008 Histochemistry and Cell Biology 129: 129-151
    Cargos and genes: insights into vesicular transport from inherited human disease.  2007 Journal of Medical Genetics 44: 545-555
4/3/08 ECM Synthesis and export during embryonic development - Part II (Ela Knapik)
  Required Readings
    Lamina-specific axonal projections in the zebrafish tectum require the type IV collagen Dragnet.  2007 Nature Neuroscience 10: 1529-1537
4/8/08 Invited Guest Speaker - Deborah Andrew, Ph.D.
Insights into Tube Size Regulation from the Drosophila Embryo
4/10/08 ECM turnover  (Jason Jessen)
  Required Readings
    Planar cell polarity genes regulate polarized extracellular matrix deposition during frog gastrulation.  2005 Current Biology 15: 787-793
    Planar polarity and tissue morphogenesis.  2007 Cell 129: 1051-1063
 

Assignment (Due 3/27/08)
Read both the paper and the review (focusing on pages 1056-1059).  You should be prepared to discuss both publication in class on Thursday.

4/15/08 Wrap up of ECM function in embryonic development (Ela Knapik)
Required Reading
    Perfusion-decellularized matrix: using nature's platform to engineer a bioartifical heart.   2008 Nature Medicine 14: 213-221
 
The Module 3 Exam is NOW available and is
DUE to Kim Kane by April 22, 2008

 

  

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 Last modified: Tuesday, April 15, 2008 by Kim.Kane@vanderbilt.edu