Henrik Boije

Project summary

Mapping new signalling pathways in treatment-resistant brain tumours

Henrik Boije aims to understand how neuronal circuits in the spinal cord are organised to enable transitions between different patterns of movement, such as creeping, walking and running. To investigate this, he studies a specific group of nerve cells, Dmrt3 neurons, using zebrafish as a model system. In the long term, this research may contribute to our understanding of the role that the breakdown of neuronal circuits plays in traumatic injuries and degenerative diseases.

 

Understanding how the nervous system develops and functions is a complex task, but studying smaller, well-defined neuronal circuits can provide insights into fundamental questions about connectivity and signalling. The aim of this project is to understand how locomotion is organised in vertebrates.

 

The motor network in the spinal cord acts like a metronome, generating rhythmic signals to the muscles and coordinating the alternation between the left and right sides of the body during movement. The link between signalling within the circuit and movement makes it possible to correlate cellular activity with behaviour. Loss of Dmrt3 interneurons results in disrupted locomotor rhythms in horses and mice. Technological advances have made zebrafish a unique model in which the development of these cells, their integration into the network and their function can be studied in vivo.

 

Dmrt3 is expressed in the zebrafish spinal cord, and preliminary data indicate that mutants exhibit motor impairments. By combining optogenetics and calcium indicators with behavioural analysis, we can investigate how Dmrt3 cells signal, how this affects surrounding cells, and the resulting effects on the animal’s movement patterns. One hypothesis is that Dmrt3 cells act as a gearbox during acceleration.

 

The project aims to link the development of a neuronal circuit to its function, both at the cellular level and at the level of the organism. Detailed knowledge of neuronal circuits is essential for improving our understanding of the role their breakdown may play in traumatic injuries and degenerative diseases.