Interplay between MIG-6/papilin and TGF-β signaling promotes extracellular matrix remodeling and modulates the maintenance of neuronal architecture

Abstract

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 in vivo quantitative imaging to determine how this mig-6-dependent fibrotic phenotype is modulated, by investigating the implication of the TGF-{beta} 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-{beta} pathway regulates ECM composition and neuronal maintenance, with MIG-6/papilin acting as a positive regulator of TGF-b 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.