RRC ID 46595
Author Gotenstein JR, Swale RE, Fukuda T, Wu Z, Giurumescu CA, Goncharov A, Jin Y, Chisholm AD.
Title The C. elegans peroxidasin PXN-2 is essential for embryonic morphogenesis and inhibits adult axon regeneration.
Journal Development
Abstract Peroxidasins form a highly conserved family of extracellular peroxidases of unknown cellular function. We identified the C. elegans peroxidasin PXN-2 in screens for mutants defective in embryonic morphogenesis. We find that PXN-2 is essential for specific stages of embryonic morphogenesis and muscle-epidermal attachment, and is also required postembryonically for basement membrane integrity. The peroxidase catalytic activity of PXN-2 is necessary for these developmental roles. pxn-2 mutants display aberrant ultrastructure of the extracellular matrix, suggesting a role in basement membrane consolidation. PXN-2 affects specific axon guidance choice points in the developing nervous system but is dispensable for maintenance of process positions. In adults, loss of pxn-2 function promotes regrowth of axons after injury, providing the first evidence that C. elegans extracellular matrix can play an inhibitory role in axon regeneration. Loss of function in the closely related C. elegans peroxidasin pxn-1 does not cause overt developmental defects. Unexpectedly, pxn-2 mutant phenotypes are suppressed by loss of function in pxn-1 and exacerbated by overexpression of wild-type pxn-1, indicating that PXN-1 and PXN-2 have antagonistic functions. These results demonstrate that peroxidasins play crucial roles in development and reveal a new role for peroxidasins as extracellular inhibitors of axonal regeneration.
Volume 137(21)
Pages 3603-13
Published 2010-11
DOI 10.1242/dev.049189
PII dev.049189
PMID 20876652
PMC PMC2964093
MeSH Aging / genetics Aging / metabolism Aging / physiology Animals Animals, Genetically Modified Axons / metabolism Axons / physiology* Caenorhabditis elegans / embryology* Caenorhabditis elegans / genetics Caenorhabditis elegans / physiology* Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism Caenorhabditis elegans Proteins / physiology* Cell Adhesion / genetics Cell Adhesion / physiology Embryo, Nonmammalian Embryonic Development / genetics Epidermis / embryology Epidermis / metabolism Epidermis / physiology Extracellular Matrix Proteins / genetics Extracellular Matrix Proteins / physiology Morphogenesis / genetics* Muscles / embryology Muscles / metabolism Nerve Regeneration / genetics* Peroxidase / genetics Peroxidase / physiology Peroxiredoxins / genetics Peroxiredoxins / metabolism Peroxiredoxins / physiology* Phylogeny
IF 5.763
Times Cited 54
C.elegans tm3464