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Cell‐specific and developmental expression of lectican‐cleaving proteases in mouse hippocampus and neocortex
Authors:C. Levy  J.M. Brooks  J. Chen  J. Su  M.A. Fox
Affiliation:1. Virginia Tech Carilion Research Institute, Roanoke, Virginia;2. Department of Biological Sciences, Virginia Tech, Blacksburg, Virginia;3. Department of Pediatrics, Virginia Tech Carilion School of Medicine, Roanoke, Virginia
Abstract:
Mounting evidence has demonstrated that a specialized extracellular matrix exists in the mammalian brain and that this glycoprotein‐rich matrix contributes to many aspects of brain development and function. The most prominent supramolecular assemblies of these extracellular matrix glycoproteins are perineuronal nets, specialized lattice‐like structures that surround the cell bodies and proximal neurites of select classes of interneurons. Perineuronal nets are composed of lecticans, a family of chondroitin sulfate proteoglycans that includes aggrecan, brevican, neurocan, and versican. These lattice‐like structures emerge late in postnatal brain development, coinciding with the ending of critical periods of brain development. Despite our knowledge of the presence of lecticans in perineuronal nets and their importance in regulating synaptic plasticity, we know little about the development or distribution of the extracellular proteases that are responsible for their cleavage and turnover. A subset of a large family of extracellular proteases (called a disintegrin and metalloproteinase with thrombospondin motifs [ADAMTS]) is responsible for endogenously cleaving lecticans. We therefore explored the expression pattern of two aggrecan‐degrading ADAMTS family members, ADAMTS15 and ADAMTS4, in the hippocampus and neocortex. Here, we show that both lectican‐degrading metalloproteases are present in these brain regions and that each exhibits a distinct temporal and spatial expression pattern. Adamts15 mRNA is expressed exclusively by parvalbumin‐expressing interneurons during synaptogenesis, whereas Adamts4 mRNA is exclusively generated by telencephalic oligodendrocytes during myelination. Thus, ADAMTS15 and ADAMTS4 not only exhibit unique cellular expression patterns but their developmental upregulation by these cell types coincides with critical aspects of neural development. J. Comp. Neurol. 523:629–648, 2015. © 2014 Wiley Periodicals, Inc.
Keywords:extracellular matrix  perineuronal net  hippocampus  neocortex  aggrecanase  ADAMTS  parvalbumin  aggrecan  RRID:nif‐0000‐00509  RRID:AB_94270  RRID:AB_2314070  RRID:AB_2068506  RRID:AB_2314535  RRID:AB_221569  RRID:AB_2278725  RRID:AB_839506  RRID:AB_570666  RRID:AB_2255374  RRID:IMSR_JAX:008069  RRID:IMSR_JAX:005630
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