Department of Neurobiology; Benard Lab
Amino Acids, Peptides, and Proteins | Developmental Biology | Developmental Neuroscience | Nervous System
Whereas remarkable advances have uncovered mechanisms that drive nervous system assembly, the processes responsible for the lifelong maintenance of nervous system architecture remain poorly understood. Subsequent to its establishment during embryogenesis, neuronal architecture is maintained throughout life in the face of the animal’s growth, maturation processes, the addition of new neurons, body movements, and aging. The C. elegans protein SAX-7, homologous to the vertebrate L1 protein family, is required for maintaining the organization of neuronal ganglia and fascicles after their successful initial embryonic development. To dissect the function of sax-7 in neuronal maintenance, we generated a null allele and sax-7S-isoform-specific alleles. We find that the null sax-7(qv30) is, in some contexts, more severe than previously described mutant alleles, and that the loss of sax-7S largely phenocopies the null, consistent with sax-7S being the key isoform in neuronal maintenance. Using a sfGFP::SAX-7S knock-in, we observe sax-7S to be predominantly expressed across the nervous system, from embryogenesis to adulthood. Yet, its role in maintaining neuronal organization is ensured by post-developmentally acting SAX-7S, as larval transgenic sax-7S(+) expression alone is sufficient to profoundly rescue the null mutants’ neuronal maintenance defects. Moreover, the majority of the protein SAX-7 appears to be cleaved, and we show that these cleaved SAX-7S fragments together, not individually, can fully support neuronal maintenance. These findings contribute to our understanding of the role of the conserved protein SAX-7/L1CAM in long-term neuronal maintenance, and may help decipher processes that go awry in some neurodegenerative conditions.
Developmental Biology, neuronal maintenance, lifelong, L1, sax-7, Ig, cleavage
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DOI of Published Version
bioRxiv 2021.01.25.428117; doi: https://doi.org/10.1101/2021.01.25.428117. Link to preprint on bioRxiv.
Now published in Genetics doi: 10.1093/genetics/iyab086
Desse VE, Blanchette CR, Perrat PN, Benard CY. (2021). Neuronal post-developmentally acting SAX-7S/L1CAM can function as cleaved fragments to maintain neuronal architecture in C. elegans [preprint]. University of Massachusetts Medical School Faculty Publications. https://doi.org/10.1101/2021.01.25.428117. Retrieved from https://escholarship.umassmed.edu/faculty_pubs/1888
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