Neuregulin 1 Type III/ErbB signaling is crucial for Schwann cell colonization of sympathetic axons

Analysis of Schwann cell (SC) development has been hampered by the lack of growing axons in many commonly used in vitro assays. As a consequence, the molecular signals and cellular dynamics of SC development along peripheral axons are still only poorly understood. Here we use a superior cervical gan...

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Hauptverfasser: Heermann, Stephan (VerfasserIn) , Hinz, Ursula (VerfasserIn) , Krieglstein, Kerstin (VerfasserIn)
Dokumenttyp: Article (Journal)
Sprache:Englisch
Veröffentlicht: December 16, 2011
In: PLOS ONE
Year: 2011, Jahrgang: 6, Heft: 12
ISSN:1932-6203
DOI:10.1371/journal.pone.0028692
Online-Zugang:Verlag, Volltext: http://dx.doi.org/10.1371/journal.pone.0028692
Verlag, Volltext: http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0028692
Volltext
Verfasserangaben:Stephan Heermann, Julia Schmücker, Ursula Hinz, Michael Rickmann, Tilmann Unterbarnscheidt, Markus H. Schwab, Kerstin Krieglstein

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520 |a Analysis of Schwann cell (SC) development has been hampered by the lack of growing axons in many commonly used in vitro assays. As a consequence, the molecular signals and cellular dynamics of SC development along peripheral axons are still only poorly understood. Here we use a superior cervical ganglion (SCG) explant assay, in which axons elongate after treatment with nerve growth factor (NGF). Migration as well as proliferation and apoptosis of endogenous SCG-derived SCs along sympathetic axons were studied in these cultures using pharmacological interference and time-lapse imaging. Inhibition of ErbB receptor tyrosine kinases leads to reduced SC proliferation, increased apoptosis and thereby severely interfered with SC migration to distal axonal sections and colonization of axons. Furthermore we demonstrate that SC colonization of axons is also strongly impaired in a specific null mutant of an ErbB receptor ligand, Neuregulin 1 (NRG1) type III. Taken together, using a novel SC development assay, we demonstrate that NRG1 type III serves as a critical axonal signal for glial ErbB receptors that drives SC development along sympathetic axons. 
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