Calcium signalling and mammary gland research

Life begins with calcium. It is the language that a sperm cell uses to respond to instructions from the female reproductive tract to alter its swimming pattern and gain the force required to penetrate the outer layers of the oocyte. The first heartbeat transpires from spontaneous calcium oscillations in embryonic cardiomyocytes. The dynamic balance of calcium between auditory hair cells and the fluid they bathe in enables us to hear our first sound and our interpretation and response to this sound requires rapid calcium flux through neuronal voltage-sensitive calcium channels. It is a signal that is capable of decoding, integrating and fine-tuning informational cues from both the chemical and mechanical microenvironment to orchestrate the form and function of many mammalian organ-systems.

In the field of epithelial developmental biology, however, there remains a major focus on signal reception (i.e. the membrane-tethered and diffusible chemical factors and their cognate receptors that spur morphogenesis) and the classical downstream intracellular pathways that drive gene transcription. Fewer studies have characterized signal transduction and integration pathways that deviate from the canonical paradigm. Indeed, the role of calcium signalling in embryonic, pubertal and gestational mammary gland development remains unexplored.

Fundamental methodological advances from our laboratory, including the development of mouse models and organoids that express genetically-encoded calcium sensors in luminal and basal epithelial lineages, have delivered important insights into functions of calcium signal oscillations in mammary gland morphogenesis and maturity.

By imaging signal-response relationships in the mammary gland across scales (cells, tissues and the organ as a whole) and utilizing computational platforms for image reconstruction and analysis, our work is providing unprecedented new insights into the molecular mechanisms that orchestrate the development and function of the namesake organ of mammals.