From spikes to intercellular waves: Tuning intercellular calcium signaling dynamics modulates organ size control

Area of Science:

• Cellular Biology
• Developmental Biology
• Biophysics

Background:

• Calcium (Ca2+) signaling dynamics are vital for intercellular communication but underlying organ-level mechanisms are unclear.
• Developing Drosophila wing imaginal discs exhibit diverse Ca2+ activity patterns, including spikes, transients, waves, and fluttering.

Purpose of the Study:

• To elucidate the biophysical mechanisms governing emergent Ca2+ signaling patterns at the organ level.
• To identify distinct cell populations and signaling pathways controlling Ca2+ dynamics in developing tissues.

Main Methods:

• Computational modeling and experimental approaches were combined.
• Identified two cell subpopulations: 'initiator cells' with high Phospholipase C (PLC) activity and 'standby cells' with baseline activity.
• Investigated the roles of hormonal stimulation, gap junctional communication, insulin, and Gαq activity.

Main Results:

• Hormonal stimulation and gap junctional communication jointly determine Ca2+ signaling patterns.
• Insulin stimulates single-cell Ca2+ spikes, while Gαq activity drives intercellular Ca2+ waves.
• A computational model successfully replicated Ca2+ transient dynamics during organ growth.
• Perturbations in Ca2+ signaling affect final organ size, indicating its role in organ size regulation.

Conclusions:

• Cytoplasmic Ca2+ acts as a dynamic reporter of tissue growth.
• Organ size regulation emerges from the interplay of growth signals and heterogeneous cell signaling states.
• This study provides a framework for further research into Ca2+ signaling and organ development.