3D epithelial cell topology tunes signaling range to promote precise patterning

Area of Science:

• Developmental Biology
• Cell Biology
• Biophysics

Background:

• Multicellular organisms coordinate cell behaviors using diffusible molecules and direct cell-cell contacts.
• Notch-Delta lateral inhibition signaling, a contact-based mechanism, patterns cell fates in developing epithelia.
• The influence of complex 3D epithelial cell shapes on cell communication and signaling range remains largely unexplored.

Purpose of the Study:

• To investigate how the three-dimensional (3D) geometry of epithelial cells influences cell communication and signaling range.
• To explore the role of cell shape and topology in patterning cell fates during development.
• To quantitatively model Notch-Delta signaling in complex 3D epithelial structures.

Main Methods:

• Development of a mathematical modeling framework (Multilayer Signaling Model) to simulate Notch-Delta signaling.
• Quantitative analysis of cell-cell contacts in 3D epithelial topologies derived from experimental data.
• In vivo perturbation of cortical stiffness and cell tortuosity in Drosophila wing margin epithelia.

Main Results:

• Epithelial cells at the Drosophila wing margin, lacking basal protrusions, contact neighbors at varying heights, increasing effective connectivity.
• The Multilayer Signaling Model predicts that lateral cell surface signaling is crucial for regulating the spacing of sensory organ precursors (SOPs).
• Experimental manipulation of cortical stiffness and cell tortuosity in vivo alters SOP spacing, confirming model predictions.

Conclusions:

• 3D cell geometry and topology play a critical role in fine-tuning the range and outcome of cell-cell signaling.
• Lateral cell surface interactions are essential for precise patterning of cell fates, such as SOP spacing.
• Understanding cell shape-dependent signaling is vital for comprehending developmental processes in multicellular organisms.