1. Neuregulin 1 type III/ErbB signaling is crucial for Schwann cell colonization of sympathetic axons.
- Author
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Heermann S, Schmücker J, Hinz U, Rickmann M, Unterbarnscheidt T, Schwab MH, and Krieglstein K
- Subjects
- Animals, Axons drug effects, Cell Movement drug effects, Cell Proliferation drug effects, Colony-Forming Units Assay, Female, Mice, Nerve Growth Factors pharmacology, Receptor Protein-Tyrosine Kinases antagonists & inhibitors, Schwann Cells drug effects, Superior Cervical Ganglion cytology, Sympathetic Nervous System cytology, Sympathetic Nervous System drug effects, Time-Lapse Imaging, Axons metabolism, Neuregulin-1 metabolism, Receptor Protein-Tyrosine Kinases metabolism, Schwann Cells cytology, Schwann Cells metabolism, Signal Transduction drug effects, Sympathetic Nervous System metabolism
- Abstract
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.
- Published
- 2011
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