Role of Neurexins in the brain and behavior

We have generated a wide diversity of neurexins mutants enabling to better study their normal and pathogenic role in human disorders.

Neurexins, a family of gene encoding cell adhesion molecules essential for the development and connectome of the brain, have been repeatedly associated with diseases of the brain such as schizophrenia (SZ) and autism (ASD). To date, the role of these genes in the onset, progress and severity of these mental disorders is still poorly understood. One of the reasons for this slow progress comes from the difficulty of properly manipulating their complex transcriptome and generating relevant models for mental health research. Additionally, considering that neurexins’ pathogenicity is most likely acting at the synaptic level, we would benefit from developing models enabling the observation of synaptic dynamics and function in real-time in a whole animal context. Whilst zebrafish is the ideal model of choice, loss-of-function (LOF) neurexin zebrafish models are currently lacking in the field.

Filling this gap, we have recently generated a series of zebrafish mutants (14) enabling to study not only the different neurexins but also the non-coding regions presenting on their genomic loci. This is the first time one can easily study those so-called “junk DNA” while there is much evidence in the literature highlighting their potential involvement in human brain development and diseases.