How Cells Shape the Developing Brain

Cell extrusion is a process where unwanted or dying cells are pushed out of a tissue to maintain its health and structure. This is essential for preventing inflammation, infection, or cancer. During embryonic development, extrusion also helps tissues and organs form correctly by removing cells that are no longer needed and allowing others to rearrange. If extrusion goes wrong, tissues can fail to develop properly or become vulnerable to disease.

A key player in this process is Erk, a signalling protein that acts like a messenger, helping cells coordinate their behaviour. Erk activity moves in waves across tissues, and these waves have been linked to extrusion events. However, scientists still do not know exactly how Erk controls extrusion during the earliest stages of brain development.

This research is led by Associate Professor Michael Smutny, Warwick Medical School, and Professor Tsuyoshi Hirashima, Yong Loo Lin School of Medicine, National University of Singapore. The project combines two powerful approaches: live imaging and computational modelling. This work can only be performed in a close partnership between the research groups and cannot be achieved in a single lab effort.

At Warwick, researchers will use zebrafish embryos, an important model for studying development, and advanced imaging tools to watch extrusion happen in real time. They will use a special biosensor that shows when Erk is active by changing its location inside the cell, along with markers for the actin cytoskeleton and cell nuclei. This will create detailed 4D movies of cells as they extrude, revealing how Erk signalling and structural changes interact.

At NUS, the team will develop artificial intelligence tools to turn these complex images into measurable data. They will reconstruct 3D views from 2D slices and build a quantitative framework that links cell behaviour, Erk signalling, and actin dynamics. This is challenging because imaging data can be incomplete or noisy, but AI and physics-based models will allow researchers to fill gaps and detect patterns that are invisible to the human eye. By integrating biology and computation, the project will uncover how molecular signals and mechanical forces work together to shape the developing brain.

This research will provide new insights into fundamental processes of development and disease, laying the groundwork for future funding and interdisciplinary innovation.