Lecture 13 - Cell Junctions and Matrix

Exam Information

  • The grading speed for Exam 1 will not be repeated for Exam 2.

  • Exam 2 will be graded by Monday with apologies for the delay.

  • Ewe, the TA, has completed the grading for multiple-choice questions. Contact her for a preliminary look at scores.

  • Upcoming classes will consist of six lectures, followed by an exam of the same format: 30 multiple-choice questions and four long-answer questions, with potential bonus questions.

Course Structure

  • The course is entering the final third, which consists of:

    • Exploring epithelial cell junctions and their role in cellular signaling.

    • A detailed analysis of the extracellular matrix (ECM) and its functions in tissue shaping.

  • Next week's focus will be two lectures on development:

    • Stem cell applications and their importance in replenishing tissues.

    • Strategies for healing and regenerating tissues based on developmental biology insights.

Cell Junctions

  • Epithelial cells form cohesive tissues through cell-cell junctions, allowing them to function as a unit.

  • The movie presented illustrates the connectivity of cells, enabling them to sculpt tissue forces, as shown during embryonic development.

Example Illustrations:

  • Cardiac Region Formation: The involution of the embryo indicates how cells change shape through internal forces.

  • Salivary Gland Development: Discusses the process of clefting, where cells change shape and form acini through cellular forces.

Morphogenesis Overview

  • Neural Tube Formation:

    • Occurs during early Xenopus development, starting from fertilization and leading to multiple rounds of cell division.

    • After gastrulation, requires transformation from a smooth ball of cells to a neural tube via neurulation.

    • The process involves:

      • Folding and elongation of embryonic structures.

      • Convergent extension, where tissue dimensions change directionally to elongate the embryo.

  • Key Processes:

    • Gastrulation: Formation of the primitive gut and shaping of the embryonic structure.

    • Neurulation: Formation of the neural tube that requires cell shape changes driven by actomyosin contractility.

Cell-Cell Junction Formation

  • Cadherins: Proteins that mediate cell adhesion and are essential for forming adherens junctions:

    • They provide connectivity between neighboring epithelial cells, associated with actomyosin networks.

    • Cadherins engage in homophilic interactions (binding to identical cadherin types), primarily needing calcium for stability and connection.

    • Discusses the mechanics of adhesion and environmental factors leading to stabilization.

Types of Junctions:

  1. Tight Junctions: Prevent movement between cells; critical for selective permeability in tissues (e.g., intestines).

  2. Adherens Junctions: Contain cadherins that link to the cytoskeleton, forming the belt of contractility.

  3. Desmosomes: Link to intermediate filaments, providing structural stability.

  4. Gap Junctions: Allow communication between adjacent cells through macromolecule exchanges.

  5. Hemidesmosomes: Connect epithelial cells to the basement membrane via intermediate filaments.

Forces in Epithelial Cells

  • Epithelial cells generate and transmit mechanical forces through actomyosin contractility.

  • Cells can dynamically adjust their adhesion based on mechanical cues from neighboring cells, showcasing a level of autonomy in tissue dynamics.

The Extracellular Matrix (ECM)

  • The ECM is a complex and dynamic structure that supports cellular organization and communication:

    • Composed of various matrix proteins, each serving unique roles:

      • Collagen: Provides structural support; different types exist for varying functions.

      • Proteoglycans: Act as space fillers and modify water retention, influencing tissue shape.

      • Glycoproteins (e.g., Fibronectin): Facilitate cell adhesion and signaling during development and healing processes.

    • Basement membrane functions as a barrier and structural support for epithelial layers, essential during pathology like cancer metastasis.

Key Concepts of ECM Dynamics

  • Proteins like laminin and collagen are integral to matrix structure, with specific binding sites allowing for complex interactions.

  • Cell signaling and mechanical forces work in tandem to modify tissue architecture, revealing the ECM’s active role in tissue development and maintenance.

  • Ghost Hearts: Demonstrates how ECM left post-cell removal can guide tissue regeneration upon reintroduction of precursor cells, underscoring the role of ECM in cellular behavior.

Practical Applications

  • Understanding of ECM roles leads to treatment strategies in regenerative medicine, especially concerning heart tissues and other organ repairs.