The PVD sensory neuron pair offer a powerful model for studying how complex dendritic trees are patterned and their structure may be modified and repaired. We previously demonstrated the cell-to-cell fusion proteins (fusogens) EFF-1 and AFF-1 play key roles in preserving the PVD structure. EFF-1 maintains PVD stereotypic dendritic shape by retracting and fusing excess branching while AFF-1 mediates aspects of its regenerative potential following injury. However, the site of action, regulation, and temporal contribution of fusogens to neuron plasticity and function remain largely unknown. Unpublished results from our lab (WBPaper00043316, WBPaper00030126) identify a candidate regulatory transcription factor, the nuclear hormone receptor NHR-25, acting upstream to
eff-1 and
aff-1 activities in PVD morphogenesis and repair. We have previously demonstrated that
nhr-25 mutants display aberrant intra-dendrite fusion events, misshaped structures, and persistent excessive outgrowth following injury. Epistatic analysis revealed that
nhr-25 influences intra-dendrite fusions by inhibiting
aff-1. In contrast,
nhr-25 activates
eff-1 to elicit pruning after injury, outgrowth, and successful regeneration. These genetic results lack spatial and temporal resolution, which we plan to address using the recently improved system for auxin-inducible degradation. By using precise tissue-specific protein depletion techniques we will assay the relative contribution of EFF-1, AFF-1 and NHR-25 to aspects of neuron morphogenesis, maintenance, and repair. We will obtain strains edited to include a degron tag on the endogenous
eff-1,
aff-1, and
nhr-25 genes. These tagged proteins will be degraded in the presence of the plant hormone auxin and an adaptor protein, TIR1. Since TIR1 is not endogenous to C. elegans, we could remove them solely in the PVD or from other specific tissues selectively expressing TIR1. Observing PVD morphogenesis and injury response and repair in the presence or absence of auxin in such strains will enable us to directly determine the spatial and temporal requirements for NHR-25 and the fusogens EFF-1 and AFF-1 in dendrite morphogenesis and repair.