Nervous system remodeling in Drosophila occurs during metamorphosis to support the transition from larval to adult-specific behaviors. The process of neuronal remodeling involves the pruning back of old dendritic and axonal connections followed by outgrowth of adult-specific arbors. Similar remodeling processes are seen throughout the animal kingdom in different developmental contexts, but the mechanisms underlying this morphological plasticity in each case remain unclear. Here, we found Split ends (SPEN) and its homolog, Spenito (NITO), are required for metamorphic remodeling of the CCAP/bursicon neurosecretory cells. SPEN and NITO belong to a well-conserved family of nuclear proteins with critical functions in transcriptional regulation and the post-transcriptional processing and nuclear export of transcripts. Cell-targeted overexpression of SPEN in CCAP/bursicon cells had no effect on the larval morphology or the pruning back of the CCAP/bursicon cell axons at the onset of metamorphosis. During the subsequent outgrowth phase of metamorphic remodeling, overexpression of either SPEN or NITO strongly inhibited axon extension, axon branching, peripheral neuropeptide accumulation, and soma growth. Cell-targeted loss-of-function manipulations for both spen and nito caused reductions in axon outgrowth, indicating that the absolute levels of SPEN and NITO activity are critical to support developmental plasticity in these neurons. Loss of spen also caused defects in central neurite pathfinding and development of boutons in peripheral axons. Although nito RNAi did not affect SPEN protein levels, the phenotypes produced by SPEN overexpression were suppressed by nito RNAi. These results suggest that SPEN and NITO function additively or synergistically in the CCAP/bursicon neurons to regulate multiple aspects of neurite outgrowth during metamorphic remodeling.