After the initial assembly of the nervous system during embryogenesis, neuronal structures need to persist lifelong for neural circuits to remain functional, in the face of maturation, growth, body movements, and aging. How the nervous system is protected throughout life is not understood. Our research using C. elegans has demonstrated that there are molecular mechanisms actively maintaining the architecture of the nervous system, which act with great cellular specificity (Benard and Hobert, 2009). In neuronal maintenance mutants that we have identified, including in the mutants
sax-7/L1CAM, neuronal structures initially develop normally, but subsequently become disorganized. Through our forward genetic screen for modifiers of
sax-7 defects, whole genome sequencing, and rescue assays, we have identified the gene
mig-6/papilin to mediate the maintenance of neuronal architecture. Indeed, loss of function of
mig-6 suppresses the progressive disorganization of
sax-7 mutants, suggesting that they play antagonistic roles. Disruption of
mig-6 function after embryogenesis alone is sufficient to suppress the defects of
sax-7 mutants, highlighting its post-developmental role in this context. Also, we find that the short, but not the long, isoform of the gene
mig-6 functions non-autonomously from body wall muscles, and that the thrombospondin type 1 domains appear important in neuronal maintenance. Furthermore, our analysis of extracellular matrix components, by confocal microscopy and FRAP assays, reveal that
mig-6 is required for the normal dynamics of collagen type IV/EMB-9 in the extracellular matrix. Thus, the impact of MIG-6 on the state of the extracellular matrix that ensheathes ganglia and fascicles may ensure a balance between the adhesion of neurons to their surrounding environment and the flexibility between them, enabling neurons to endure lifelong stress. Understanding general principles of the maintenance of neuronal architecture may help identify key factors influencing the onset and progression of neurodegenerative conditions.