Cell Differentiation and Adhesion Dynamics 1955

Townes and Holtfreter 1955

• Demonstrated that even in the neurula stage, presumptive cells have already differentiated, capable of segregating into separate structural cell groupings after disaggregation.
• Cells display enough differentiation to segregate after disaggregation.

Cell Adhesion

• Selective Affinity
• Inner surface of the ectoderm (+) affinity for mesodermal cells
• Inner surface of the ectoderm (-) affinity for endodermal cells
• Mesoderm (+) affinity for both ectodermal and endodermal cells
• Axial mesoderm gives rise to the notochord.

Thermodynamic Model of Cell Interactions

• Cells do not sort randomly.
• Cells actively move to create tissue organization.
• Differential adhesion hypothesis: attempts to explain cell sorting patterns based on thermodynamic principles.
• Malcolm Steinberg's Experiments: Certain cell types move centrally when combined with some cell types, but migrate peripherally when combined with others.

Importance of Cadherins

• Cadherin expression correlates with surface tension.
• Cell sorting hierarchy is based on cadherin interactions.
• The type of cadherin is important in development.
• R-cadherin and B-cadherin don’t bind well together.
• N-cadherin is crucial for separating neural precursors.
• Blocking N-cadherin in neural precursors disrupts the formation of the border between the skin and nervous system.

Cell Migration

• Common for both mesenchymal and epithelial cells.
• Significant movement during gastrulation to form the three germ layers.
• Polarization: a cell defines its front and back.
• Polarization can be directed by diffusing signals or signals from the extracellular matrix.
• These signals reorganize the cytoskeleton.

Integrins

• Span the cell membrane, connecting extracellular matrix to the actin cytoskeleton.
• Forms focal adhesion on the cell membrane where the membrane contacts the extracellular matrix.

Cell Signaling

• Regulates adhesion, migration, differentiation, and division.
• Signals from one cell are received by another cell.

Eye Development

• Development of the vertebrate eye is an example of one group of cells changing the behavior of an adjacent group.
• Induction: a close-range interaction where one group of cells induces changes in another.

Hierarchy of Cell Sorting

• Cells interact to form an aggregate with the smallest interfacial energy.
• The most thermodynamically stable pattern is preferred.

Cadherins and Cell Adhesion

• Boundaries between tissues are created by different cell types having different types and amounts of cell adhesion molecules.
• Cadherins are the major cell adhesion molecules.

Cadherins

• Calcium-dependent adhesion molecules.
• Transmembrane proteins interacting with other cadherins on adjacent cells.
• Anchored inside the cell by a complex of proteins called catenins.

Cadherin & Catenin Binding to Actin

• Provides structural integrity and helps regulate cell shape and movement.

Interference with Cadherin Function

• Disrupts cell-cell adhesion and tissue organization.

Maternal Cadherin mRNA

• If attacked, it disrupts the development of cell-cell adhesion and embryos may fail to develop normally.

Cadherin Functions

• Adherence of cells together.
• Link to and assembles the actin cytoskeleton.
• Signaling molecules that alter a cell’s gene expression.

Types of Cadherins

• E-cadherin: expressed on early mammalian cells (zygote stage), important for epithelial cell junctions.
• P-cadherin: found primarily in placenta, helps attach the placenta to the uterus.
• N-cadherin: highly expressed on cells of the developing CNS, critical for neural tissue organization.
• R-cadherin: important for retinal formation.

Protocadherins

• Do not connect to the actin skeleton through catenins.
• Expressing similar protocadherins helps keep migrating epithelial cells together.
• Their role in cell-cell adhesion and tissue development is not as well-understood as other cadherin types.

Explore the findings of Townes and Holtfreter in 1955 regarding cell differentiation and adhesion. This quiz covers selective affinity between ectoderm, mesoderm, and endoderm cells, and the thermodynamic model explaining cell sorting. Test your knowledge on the differential adhesion hypothesis and its implications for tissue organization.