Meningeal cell-derived semaphorin 3A inhibits neurite outgrowth

Simone P. Niclou*, Elske H.P. Franssen, Erich M.E. Ehlert, Masahiko Taniguchi, Joost Verhaagen

*Corresponding author for this work

Research output: Contribution to journalArticleResearchpeer-review

89 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)902-912
Number of pages11
JournalMolecular and Cellular Neurosciences
Issue number4
Publication statusPublished - Dec 2003
Externally publishedYes


Dive into the research topics of 'Meningeal cell-derived semaphorin 3A inhibits neurite outgrowth'. Together they form a unique fingerprint.

Cite this