How do calcium transients shape brain function during early neurogenesis?

Purpose and goal:

The overall aim of this project was to understand how Ca2+ transients and their signalling pathways affect early neurogenesis and underlie severe brain disorders. To this end, patient and control induced pluripotent stem cell derived models of early neurogenesis where used to: 1. Identify the time course and type of Ca2+ fluxes present in iPSCs and over early neural differentiation.

2. The role of cell-adhesion molecules in regulating Ca2+ fluxes at different stages of neurogenesis and their correlation with cell-fate. 3. The contribution of the above mechanisms to brain disorders. Expected results and effects:

The results obtained in this project increased our understanding of how Ca2+ signaling contributes to the maintenance and derivation of human iPSCs for disease modeling, how Ca2+ signaling affects early human brain development and how their defects underlie developmental brain disorders. It further aided in the standardisation of hiPSC cultures, and providing researchers with key tools for the application of hiPSCs in neuropharmacological studies, disease modelling and stem-cell therapies.

Approach and implementation:

The preliminary data obtained on the project will be used to acquire funding to further explore the role of cell-adhesion molecules and calcium signalling in cell-fate specification during early neurogenesis on molecular level and in animal models. Further contact with the clinic, will help us to explore the translational value of the findings and recruit more neurodevelopment disorder patients with defects in genes found in the identified signalling pathways.

This could pave the way for developing personalised therapeutics in this large group of currently untreatable disorders.