Proper function of the motor unit is dependent upon the correct development of dendrites and axons. The infant/childhood onset
motoneuron disease spinal muscular atrophy (SMA), caused by low levels of the survival motor neuron (SMN) protein, is characterized
by muscle denervation and paralysis. Although different SMA models have shown neuromuscular junction defects and/or motor
axon defects, a comprehensive analysis of motoneuron development in vivo under conditions of low SMN will give insight into
why the motor unit becomes dysfunctional. We have generated genetic mutants in zebrafish expressing low levels of SMN from
the earliest stages of development. Analysis of motoneurons in these mutants revealed motor axons were often shorter and had
fewer branches. We also found that motoneurons had significantly fewer dendritic branches and those present were shorter.
Analysis of motor axon filopodial dynamics in live embryos revealed that mutants had fewer filopodia and their average half-life
was shorter. To determine when SMN was needed to rescue motoneuron development, SMN was conditionally induced in smn mutants during embryonic stages. Only when SMN was added back soon after motoneurons were born could later motor axon development
be rescued. Importantly, analysis of motor behavior revealed that animals with motor axon defects had significant deficits
in motor output. We also show that SMN is required earlier for motoneuron development than for survival. These data support
that SMN is needed early in development for motoneuron dendrites and axons to develop normally and that this is essential
for proper connectivity and movement.