The extracellular-matrix protein matrilin 2 participates in peripheral nerve regeneration.
The extracellular-matrix protein matrilin 2 participates in peripheral nerve regeneration.
Matrilins are adaptor proteins of the extracellular matrix involved in the formation of both collagen-dependent and collagen-independent filamentous networks. Although their molecular structure and binding partners have been characterized, the functional roles of the four matrilin family members in vivo are still largely unknown. Here, we show that matrilin 2, expressed in pre-myelinating Schwann cells during normal development, profoundly influences the behaviour of glial cells and neurons in vitro. When offered as a uniform substrate, matrilin 2 increased neurite outgrowth of dorsal root ganglia (DRG) neurons and enhanced the migration of both cell line- and embryonic DRG-derived Schwann cells. Vice versa, axonal outgrowth and cell migration were decreased in DRG cultures prepared from matrilin-2-deficient mice compared with wild-type (wt) cultures. In stripe assays, matrilin 2 alone was sufficient to guide axonal growth and, interestingly, axons favoured the combination of matrilin 2 and laminin over laminin alone. In vivo, matrilin 2 was strongly upregulated in injured peripheral nerves of adult wild-type mice and failure of protein upregulation in knockout mice resulted in delayed regrowth of regenerating axons and delayed time-course of functional recovery. Strikingly, the functional recovery 2 months after nerve injury was inferior in matrilin-2-deficient mice compared with wild-type littermates, although motoneuron survival, quality of axonal regeneration, estimated by analyses of axonal diameters and degrees of myelination, and Schwann cell proliferation were not influenced by the mutation. These results show that matrilin 2 is a permissive substrate for axonal growth and cell migration, and that it is required for successful nerve regeneration.
schwann cells, axonal outgrowth, extracellular matrix, coating substrates, cell migration, peripheral nerve regeneration
995-1004
Malin, Dmitry
49c958a8-e39d-4e79-961f-28ed441e05df
Sonnenberg-Riethmacher, Eva
6da24b56-bcab-43c2-8da3-01c99f274f1d
Guseva, Daria
73c59b39-125d-4ccb-8079-24c8c14eb39b
Wagener, Raimund
401930b6-9833-4d2f-81d0-fc3b1ae020bd
Aszódi, Attila
00e6c7c8-69c6-44a6-9486-1dbb052374a2
Irintchev, Andrey
a98ed72e-bc50-40ee-bb91-75e44a64c319
Riethmacher, Dieter
1a0a0c2e-e94d-4d0a-a890-90107a2545bc
University of Southampton
18 March 2009
Malin, Dmitry
49c958a8-e39d-4e79-961f-28ed441e05df
Sonnenberg-Riethmacher, Eva
6da24b56-bcab-43c2-8da3-01c99f274f1d
Guseva, Daria
73c59b39-125d-4ccb-8079-24c8c14eb39b
Wagener, Raimund
401930b6-9833-4d2f-81d0-fc3b1ae020bd
Aszódi, Attila
00e6c7c8-69c6-44a6-9486-1dbb052374a2
Irintchev, Andrey
a98ed72e-bc50-40ee-bb91-75e44a64c319
Riethmacher, Dieter
1a0a0c2e-e94d-4d0a-a890-90107a2545bc
Malin, Dmitry, Sonnenberg-Riethmacher, Eva, Guseva, Daria, Wagener, Raimund, Aszódi, Attila, Irintchev, Andrey and Riethmacher, Dieter
,
University of Southampton
(2009)
The extracellular-matrix protein matrilin 2 participates in peripheral nerve regeneration.
Journal of Cell Science, 122 (7), .
(doi:10.1242/jcs.040378).
Abstract
Matrilins are adaptor proteins of the extracellular matrix involved in the formation of both collagen-dependent and collagen-independent filamentous networks. Although their molecular structure and binding partners have been characterized, the functional roles of the four matrilin family members in vivo are still largely unknown. Here, we show that matrilin 2, expressed in pre-myelinating Schwann cells during normal development, profoundly influences the behaviour of glial cells and neurons in vitro. When offered as a uniform substrate, matrilin 2 increased neurite outgrowth of dorsal root ganglia (DRG) neurons and enhanced the migration of both cell line- and embryonic DRG-derived Schwann cells. Vice versa, axonal outgrowth and cell migration were decreased in DRG cultures prepared from matrilin-2-deficient mice compared with wild-type (wt) cultures. In stripe assays, matrilin 2 alone was sufficient to guide axonal growth and, interestingly, axons favoured the combination of matrilin 2 and laminin over laminin alone. In vivo, matrilin 2 was strongly upregulated in injured peripheral nerves of adult wild-type mice and failure of protein upregulation in knockout mice resulted in delayed regrowth of regenerating axons and delayed time-course of functional recovery. Strikingly, the functional recovery 2 months after nerve injury was inferior in matrilin-2-deficient mice compared with wild-type littermates, although motoneuron survival, quality of axonal regeneration, estimated by analyses of axonal diameters and degrees of myelination, and Schwann cell proliferation were not influenced by the mutation. These results show that matrilin 2 is a permissive substrate for axonal growth and cell migration, and that it is required for successful nerve regeneration.
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More information
Submitted date: July 2008
Published date: 18 March 2009
Additional Information:
Matrilin 2 hits a nerve
Matrilins 1-4 are extracellular-matrix proteins that are
involved in the formation of collagen-dependent and
collagen-independent filamentous networks, but their
specific functions are mostly unknown. In this study,
Dieter Riethmacher and colleagues (p. 995) study
matrilin-2-deficient mice (which were previously found to have a normal
phenotype) to investigate whether matrilin 2 is important in nervous tissue,
in which it is reportedly expressed. They show that matrilin 2 is expressed
in mouse Schwann cells (SCs) during development and following
peripheral-nerve injury in adult mice. Two types of migration assays reveal
that matrilin-2-deficient SCs have defective migration and adhesion abilities
in vitro. In addition, they report the remarkable finding that matrilin 2
supports axonal growth in vitro as efficiently as laminin, the most potent
known enhancer of axonal growth. In vivo experiments show that, although
matrilin 2 is expressed at low levels in adult mice, its expression is induced
following peripheral-nerve injury. Furthermore, nerve regeneration
following injury was slowed in matrilin-2-deficient mice. These findings
characterise a novel SC-derived factor that is important for optimal
peripheral-nerve regeneration.
Keywords:
schwann cells, axonal outgrowth, extracellular matrix, coating substrates, cell migration, peripheral nerve regeneration
Identifiers
Local EPrints ID: 66666
URI: http://eprints.soton.ac.uk/id/eprint/66666
ISSN: 0021-9533
PURE UUID: 0e73aee7-a540-4e7e-ac68-e5519ae50e31
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Date deposited: 07 Jul 2009
Last modified: 14 Mar 2024 02:53
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Contributors
Author:
Dmitry Malin
Author:
Eva Sonnenberg-Riethmacher
Author:
Daria Guseva
Author:
Raimund Wagener
Author:
Attila Aszódi
Author:
Andrey Irintchev
Author:
Dieter Riethmacher
Corporate Author: University of Southampton
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