title: Mouse schwann cells need both NRG1 and cyclic AMP to myelinate.
abstract: Genetically modified mice have been a major source of information about the molecular control of Schwann-cell myelin formation, and the role of β-neuregulin 1 (NRG1) in this process in vivo. In vitro, on the other hand, Schwann cells from rats have been used in most analyses of the signaling pathways involved in myelination. To correlate more effectively in vivo and in vitro data, we used purified cultures of mouse Schwann cells in addition to rat Schwann cells to examine two important myelin-related signals, cyclic adenosine monophosphate (cAMP), and NRG1 and to determine whether they interact to control myelin differentiation. We find that in mouse Schwann cells, neither cAMP nor NRG1, when used separately, induced markers of myelin differentiation. When combined, however, they induced strong protein expression of the myelin markers, Krox-20 and P(0) . Importantly, the level of cAMP signaling was crucial in switching NRG1 from a proliferative signal to a myelin differentiation signal. Also in cultured rat Schwann cells, NRG1 promoted cAMP-induced Krox-20 and P(0) expression. Finally, we found that cAMP/NRG1-induced Schwann-cell differentiation required the activity of the cAMP response element binding family of transcription factors in both mouse and rat cells. These observations reconcile observations in vivo and on neuron-Schwann-cell cultures with studies on purified Schwann cells. They demonstrate unambiguously the promyelin effects of NRG1 in purified cells, and they show that the cAMP pathway determines whether NRG1 drives proliferation or induces myelin differentiation.
authors.affiliation: Department of Cell and Developmental Biology, University College London, Gower Street, London WC1E 6BT, United Kingdom.
authors.forename: Peter
authors.initials: P
authors.lastname: Arthur-Farraj
authors.forename: Katharina
authors.initials: K
authors.lastname: Wanek
authors.forename: Janina
authors.initials: J
authors.lastname: Hantke
authors.forename: Catherine M
authors.initials: CM
authors.lastname: Davis
authors.forename: Anuj
authors.initials: A
authors.lastname: Jayakar
authors.forename: David B
authors.initials: DB
authors.lastname: Parkinson
authors.forename: Rhona
authors.initials: R
authors.lastname: Mirsky
authors.forename: Kristján R
authors.initials: KR
authors.lastname: Jessen
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D015153:Blotting, Western; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism* / Q000494:pharmacology; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D051379:Mice; D018993:Myelin P0 Protein / Q000378:metabolism; D009186:Myelin Sheath / Q000187:drug effects / Q000378:metabolism*; D020890:Neuregulin-1 / Q000378:metabolism* / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012583:Schwann Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D012584:Sciatic Nerve / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology
chemical_list: D018993:Myelin P0 Protein; D020890:Neuregulin-1; C490581:Nrg1 protein, mouse; D000242:Cyclic AMP