Article (Scientific journals)
Meningeal cell-derived semaphorin 3A inhibits neurite outgrowth.
NICLOU, Simone P.; Franssen, Elske H P; Ehlert, Erich M E et al.
2003In Molecular and Cellular Neuroscience, 24 (4), p. 902-12
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Keywords :
Growth Inhibitors; Semaphorin-3A; Animals; Cells, Cultured; Ganglia, Spinal/embryology/growth & development/metabolism; Growth Cones/metabolism; Growth Inhibitors/biosynthesis/deficiency/genetics; Meninges/cytology/embryology/growth & development/metabolism; Mice; Mice, Inbred C57BL; Mice, Knockout; Neural Inhibition/physiology; Neurites/metabolism; Rats; Semaphorin-3A/biosynthesis/deficiency/genetics
Abstract :
[en] The neural scar that forms after injury to the mammalian central nervous system is a barrier to sprouting and regenerating axons. In addition to reactive astrocytes that are present throughout the lesion site, leptomeningeal fibroblasts invade the lesion core. When isolated in vitro, these cells form a very poor substrate for growing neurites, even more so than reactive astrocytes. Nevertheless the molecular mechanisms involved in this growth inhibition are not well understood. Semaphorins have been reported to be upregulated in meningeal cells (MCs) on mechanical injury to the brain and spinal cord. In the present study, we show that Sema3A mRNA and active protein are produced by cultured meningeal cells. A protein extract from these cells induces the collapse of embryonic dorsal root ganglion (DRG) growth cones. This collapsing activity is partially blocked by neuropilin-1 antibodies and is absent in meningeal cells derived from Sema3A-knockout mice. In addition to growth cone collapse, recombinant Sema3A but not Sema3C inhibits neurite outgrowth of embryonic DRGs. Consistent with this result we find that the inhibitory effect of meningeal cells on neurite outgrowth is partially overcome on Sema3A-deficient MCs. Furthermore we show that the inhibitory effect of MC-derived Sema3A on neurite outgrowth is modulated by nerve growth factor. Our results show that Sema3A, a chemorepellent during nervous system development, is a major neurite growth-inhibitory molecule in meningeal fibroblasts and is therefore likely to contribute to the inhibitory properties of the neural scar.
Disciplines :
Oncology
Author, co-author :
NICLOU, Simone P. ;  Graduate School of Neurosciences Amsterdam, Netherlands Institute for Brain Research, Meibergdreef 33, 1105 AZ Amsterdam, The Netherlands. s.niclou@nih.knaw.nl
Franssen, Elske H P
Ehlert, Erich M E
Taniguchi, Masahiko
Verhaagen, Joost
External co-authors :
yes
Language :
English
Title :
Meningeal cell-derived semaphorin 3A inhibits neurite outgrowth.
Publication date :
December 2003
Journal title :
Molecular and Cellular Neuroscience
ISSN :
1044-7431
eISSN :
1095-9327
Publisher :
Elsevier, United States
Volume :
24
Issue :
4
Pages :
902-12
Peer reviewed :
Peer Reviewed verified by ORBi
Available on ORBilu :
since 19 February 2024

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