The extracellular matrix protein MIG-6/papilin mediates the maintenance of neuronal architecture

The extracellular matrix protein MIG-6/papilin mediates the maintenance of neuronal architecture

Malika Nadour*, Marie Biard, Lise Rivollet*, Andrea Thackeray^, Philippe St-Louis*, Claire Bénard*^

*Dept Biological Sciences, CERMO-FC Research Center, Université du Québec à Montréal, Canada
^Dept Neurobiology, University of Massachusetts Medical School, USA

After the initial assembly of the nervous system during embryogenesis, neuronal circuits 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, in cell-specific manner, the architecture of the nervous system (Bénard and Hobert, 2009). Through our genetic screen, we identified the gene mig-6/papilin to mediate neuronal maintenance: loss of function of mig-6/papilin after embryogenesis is sufficient to suppresses the progressive disorganization of sax-7/L1CAM mutants defects, suggesting antagonistic roles and highlighting post-developmental role of mig-6 in this context. We also find that mig-6 function depends on the gene mig-17 encoding a secreted ADAMTS enzyme. Our confocal microscopy analysis of extracellular matrix (ECM) reveals abnormal accumulations of collagen type IV/EMB-9 and laminin. Thus, MIG-6/Papilin’s impact on the state of the ECM that ensheathes ganglia and fascicles may ensure a balance of adhesion and flexibility between neurons and their surrounding environment, enabling neuronal circuits to endure lifelong stress. Mutations in ECM genes cause a wide range of rare genetic connective tissues disorders as corneal dystrophies, muscular dystrophy and geleophysic dysplasia (Hubmacher et al, 2015; Lamandé and Bateman 2019). Understanding general principles of the maintenance of neuronal architecture and connectivity may help identify key factors influencing the onset and progression of neurodegenerative conditions and understand the molecular pathogenesis of some rare diseases.