Lateralized Tenm4 expression biases visual performance and modulates axonal growth and pre-synapse size in retinal ganglion cells

The precise wiring of neuronal connections is a striking feature of the central nervous system and is critical for correct brain function. During vertebrate visual development, retinal ganglion cells (RGCs) establish synaptic connections with postsynaptic cells in the optic tectum, a process that is in part conferred by cell adhesion molecules. However, a complete understanding of the retinotectal wiring mechanism is lacking. Here, we show that the synaptic adhesion molecule Teneurin-4 (Tenm4) is expressed by RGCs and their postsynaptic tectal cell targets in a left-right side-specific manner in zebrafish. Loss of tenm4 leads to defects in presynaptic structures in RGCs and further affects their axonal growth and arbor complexity. Functional assessment of RGC responses to visual stimuli showed a general increase in response amplitude in mutant animals. Visual behavioral analysis revealed a deficit with a strong left-right asymmetrical component in mutant larvae. Our findings demonstrate that tenm4 plays an important role in sensorimotor circuit assembly, extending to neural activities and visual acuity.