Synchronization of the segmentation clock using synthetic cell-cell signaling

Area of Science:

• Developmental Biology
• Systems Biology
• Synthetic Biology

Background:

• The segmentation clock, involving oscillatory gene expression in the presomitic mesoderm (PSM), drives somite formation during vertebrate development.
• Delta-Notch signaling synchronizes these oscillations at the population level, with its inhibition leading to somite fusion.
• The precise mechanisms by which cell-cell signaling couples and synchronizes oscillatory gene expression remain incompletely understood.

Purpose of the Study:

• To investigate how synthetic cell-cell signaling can induce synchronized oscillations in PSM organoids.
• To elucidate the role of intracellular domains of synthetic ligands in cell-cell communication.
• To determine if synthetic signaling can restore synchronized oscillations in cells lacking functional Delta-Notch signaling.

Main Methods:

• Generation of PSM organoids.
• Implementation of synthetic cell-cell signaling using designed ligand-receptor pairs.
• Optogenetic assays to probe intracellular signaling dynamics.
• Assessment of oscillatory gene expression and synchronization in manipulated PSM cells.

Main Results:

• Synthetic cell-cell signaling successfully induced synchronized oscillations in PSM organoids.
• Optogenetic experiments revealed the critical role of synthetic ligand intracellular domains in dynamic communication.
• Oscillatory synthetic coupling restored synchronized gene expression in Delta-Notch signaling-deficient PSM cells.
• Non-oscillatory synthetic coupling failed to restore synchronization.

Conclusions:

• Ligand-receptor molecules play a crucial role in coordinating segmentation clock synchronization.
• Synthetic cell-cell signaling provides a novel method to program temporal gene expression in organoids and artificial tissues.
• This study offers insights into the fundamental mechanisms governing biological oscillations and tissue patterning.