An instructive role for the interstitial matrix in tissue patterning: tissue segregation and intercellular invasion.

Area of Science:

• Developmental Biology
• Cell Biology
• Tissue Engineering

Background:

• Intercellular invasion is cell movement into adjacent tissues, contrasting with tissue segregation where boundaries are maintained.
• The developing avian heart exhibits distinct interfaces between mesenchymal and myocardial tissues, with some showing planar segregation and others diffuse invasion.
• Understanding the mechanisms governing invasion and segregation is crucial for comprehending tissue development and organization.

Purpose of the Study:

• To investigate the role of the interstitial matrix in intercellular invasion and tissue segregation in the developing heart.
• To model and analyze the conditions that promote or inhibit tissue sorting and cell intermingling.
• To elucidate the molecular mechanisms underlying the differential behavior of mesenchymal and myocardial cells at tissue interfaces.

Main Methods:

• Organ culture of avian heart tissues (mesenchymal and myocardial cells) to observe invasion and segregation.
• Formation of chimeric tissue reaggregates by fusing cell aggregates to study sorting mechanisms.
• Analysis of fibronectin distribution and its correlation with cell movement and matrix deposition.
• Pharmacological manipulation using peptides (GRGDSP) to assess the role of fibronectin adhesion sites.

Main Results:

• Invasion and segregation coexist in different regions of the developing heart.
• A fibronectin-rich interstitial matrix, elaborated by cardiac mesenchyme, is critical for both invasion and segregation.
• Matrix deposition is essential for tissue sorting; its absence prevents segregation.
• Matrix redistribution precedes invasion, with matrix-poor regions facilitating cell movement across tissue boundaries.
• The fibronectin adhesion site peptide GRGDSP reversibly blocks tissue sorting.

Conclusions:

• The fibronectin-rich interstitial matrix plays a pivotal role in regulating intercellular invasion and tissue segregation during heart development.
• Differential matrix deposition and redistribution are key determinants of cell behavior and tissue boundary formation.
• Targeting fibronectin-mediated adhesion offers potential for controlling tissue interactions and organization.