title: Neuregulin 1 type III/ErbB signaling is crucial for Schwann cell colonization of sympathetic axons.
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.
authors.affiliation: Department of Neuroanatomy, University of Heidelberg, Heidelberg, Germany. stephan.heermann@cos.uni-heidelberg.de
authors.forename: Stephan
authors.initials: S
authors.lastname: Heermann
authors.forename: Julia
authors.initials: J
authors.lastname: Schmücker
authors.forename: Ursula
authors.initials: U
authors.lastname: Hinz
authors.forename: Michael
authors.initials: M
authors.lastname: Rickmann
authors.forename: Tilmann
authors.initials: T
authors.lastname: Unterbarnscheidt
authors.forename: Markus H
authors.initials: MH
authors.lastname: Schwab
authors.forename: Kerstin
authors.initials: K
authors.lastname: Krieglstein
mesh_terms: D000818:Animals; D001369:Axons / Q000187:drug effects / Q000378:metabolism*; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D003114:Colony-Forming Units Assay; D005260:Female; D051379:Mice; D009414:Nerve Growth Factors / Q000494:pharmacology; D020890:Neuregulin-1 / Q000378:metabolism*; D020794:Receptor Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D012583:Schwann Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D017783:Superior Cervical Ganglion / Q000166:cytology; D013564:Sympathetic Nervous System / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D059008:Time-Lapse Imaging
chemical_list: D009414:Nerve Growth Factors; D020890:Neuregulin-1; D020794:Receptor Protein-Tyrosine Kinases