Wild-type zebrafish larval hindbrain, showing the paired Mauthner cells (M) and the rhombomere 3 commissures (arrows). Image courtesy of Michael Granato, University of Pennsylvania School of Medicine, Philadelphia, USA.

Different types of motor behaviour are regulated by specific neuronal circuits that are very precisely constructed during development. Although lesion and mutation studies have helped to identify some of these circuits in vertebrates, it has proved more difficult to elucidate the roles of individual neuronal components. The zebrafish is a useful model for analysing motor circuits, because its nervous system is assembled in a highly stereotypical manner and the locations of different neuronal subtypes are very well defined. As reported in Development, Lorent et al. have used this model to identify a gene that is required for one particular type of motor behaviour and seems to be essential for axonal pathfinding during development of the underlying neuronal circuit.

The space cadet gene emerged from a screen for mutations that affect specific aspects of motor behaviour in zebrafish. The mutation was initially characterized by the failure of larvae to show an escape response, which requires them to make a fast 180° turn. The main anatomical defect was the absence of two rhombomere 3 commissures. The authors showed that it was possible to generate a phenocopy of the space cadet mutant behaviour by severing the rhombomere 3 commissural tracts in wild-type larvae, confirming a causal relationship between the defects in commissure development and the behavioural phenotype. They narrowed the defect down further to a specific class of cell — the spiral fibre neurons. These neurons synapse onto Mauthner neurons, which were already known to be involved in regulating the escape response. By retrograde labelling of the Mauthner neurons with neurobiotin, which is able to pass through electrical synapses, they showed that the spiral fibre neurons failed to form synapses with the Mauthner neurons in the space cadet mutants.

What role does the space cadet gene play in neural development? One clue came from the observation that the pathfinding of another class of neuron was affected in the mutants — the retinal ganglion cells (RGCs). RGCs share certain features with spiral fibre neurons; for both cells, axonogenesis occurs relatively late during development, and their axons establish new commissural paths instead of extending into pre-existing trajectories. Lorent et al. propose that the product of the space cadet gene is required for the formation of late-developing commissures and could have a role in pioneering new axonal trajectories.

So, Lorent et al. have shown that the spiral fibre neurons are an important component of the motor circuit that underlies fast turning movements in zebrafish. They also provide a rare example of a single gene mutation that profoundly affects a specific motor response, and it will be very interesting to find out what type of factor is encoded by the space cadet gene.