Neuronal architecture laid out during embryogenesis persists lifelong, ensuring normal nervous system function. However, the mechanisms underlying the long-term maintenance of neuronal organization remain largely unknown. We previously uncovered that the conserved extracellular matrix protein MIG-6/papilin impacts collagen IV remodeling and neuronal maintenance, such that disruption of MIG-6/papilin leads to a collagen IV fibrotic state and altered tissue biomechanics, thereby stabilizing neuronal architecture. Here, we combine incisive molecular genetics and quantitative imaging to determine how this -dependent fibrotic phenotype is modulated, by investigating the implication of the TGF-β pathway, which is well known to regulate fibrosis in mammals. Our findings highlight a mechanism whereby the interplay between MIG-6/papilin and the TGF-β pathway regulates ECM composition and neuronal maintenance, with MIG-6/papilin acting as a positive regulator of TGF-β signaling. This work provides key insights into the molecular basis of sustaining neuronal architecture and offers a foundation for understanding age-related neurodegenerative and fibrotic conditions.