title: Canonical Wnt signalling requires the BMP pathway to inhibit oligodendrocyte maturation.
abstract: OLs (oligodendrocytes) are the myelinating cells of the CNS (central nervous system), wrapping axons in conductive sheathes to ensure effective transmission of neural signals. The regulation of OL development, from precursor to mature myelinating cell, is controlled by a variety of inhibitory and inductive signalling factors. The dorsal spinal cord contains signals that inhibit OL development, possibly to prevent premature and ectopic precursor differentiation. The Wnt and BMP (bone morphogenic protein) signalling pathways have been identified as dorsal spinal cord signals with overlapping temporal activity, and both have similar inhibitory effects on OL differentiation. Both these pathways feature prominently in many developmental processes and demyelinating events after injury, and they are known to interact in complex inductive, inhibitive and synergistic manners in many developing systems. The interaction between BMP and Wnt signalling in OL development, however, has not been extensively explored. In the present study, we examine the relationship between the canonical Wnt and BMP pathways. We use pharmacological and genetic paradigms to show that both Wnt3a and BMP4 will inhibit OL differentiation in vitro. We also show that when the canonical BMP signalling pathway is blocked, neither Wnt3a nor BMP4 have inhibitory effects on OL differentiation. In contrast, abrogating the Wnt signalling pathway does not alter the actions of BMP4 treatment. Our results indicate that the BMP signalling pathway is necessary for the canonical Wnt signalling pathway to exert its effects on OL development, but not vice versa, suggesting that Wnt signals upstream of BMP.
authors: Department of Neurology, Childrens Hospital of Philadelphia, Philadelphia, PA, U.S.A.
authors: Keith
authors: K
authors: Feigenson
authors: Mary
authors: M
authors: Reid
authors: Jill
authors: J
authors: See
authors: E Bryan
authors: EB
authors: Crenshaw III
authors: Judith B
authors: JB
authors: Grinspan
references: J Biol Chem. 2003 Dec 5;278(49):48805-14
references: 14551209
references: J Neurotrauma. 2009 Jul;26(7):955-64
references: 19473059
references: Stem Cells. 2007 Dec;25(12):3204-14
references: 17872503
references: Development. 1993 Feb;117(2):525-33
references: 8330523
references: Development. 2004 Sep;131(17):4131-42
references: 15280210
references: Cell Res. 2009 Jan;19(1):71-88
references: 19002158
references: J Neurosci Res. 2004 Jun 1;76(5):593-8
references: 15139018
references: Genes Dev. 2002 Mar 1;16(5):548-53
references: 11877374
references: Genes Dev. 2003 Aug 15;17(16):1963-8
references: 12923052
references: Proc Natl Acad Sci U S A. 1982 Apr;79(8):2709-13
references: 7045870
references: Genes Dev. 1995 Dec 15;9(24):3027-37
references: 8543149
references: Development. 2008 Nov;135(22):3801-11
references: 18927151
references: Development. 2001 Feb;128(4):551-60
references: 11171338
references: J Neuropathol Exp Neurol. 2009 Jun;68(6):595-604
references: 19458544
references: Dev Biol. 2005 Jun 15;282(2):397-410
references: 15950605
references: J Neurochem. 2010 Oct;115(1):11-22
references: 20193041
references: Dev Biol. 2000 Nov 1;227(1):42-55
references: 11076675
references: Cell. 2007 Nov 30;131(5):980-93
references: 18045539
references: Proc Natl Acad Sci U S A. 2008 Nov 4;105(44):16970-5
references: 18957545
references: J Neurosci Res. 1995 Jul 1;41(4):540-51
references: 7473886
references: Proc Natl Acad Sci U S A. 2000 Jul 18;97(15):8358-63
references: 10890911
references: Nat Neurosci. 2006 Feb;9(2):173-9
references: 16388308
references: Glia. 2006 Sep;54(4):285-96
references: 16862533
references: J Neurosci. 2002 Dec 1;22(23):10333-45
references: 12451133
references: Prog Neuropsychopharmacol Biol Psychiatry. 2009 Apr 30;33(3):503-10
references: 19439244
references: Nat Genet. 2003 Mar;33(3):366-74
references: 12590258
references: N Engl J Med. 1998 Jan 29;338(5):278-85
references: 9445407
references: Dev Dyn. 2008 Nov;237(11):3324-31
references: 18924237
references: Genes Dev. 2009 Jul 1;23(13):1571-85
references: 19515974
references: Nat Neurosci. 2009 Jul;12(7):829-38
references: 19503085
references: Dev Biol. 2007 Mar 1;303(1):181-90
references: 17150208
references: Dev Biol. 2004 Mar 1;267(1):242-51
references: 14975730
references: Nat Neurosci. 2010 May;13(5):541-550
references: 20418875
references: Cancer Biol Ther. 2002 Nov-Dec;1(6):640-5
references: 12642687
references: Development. 2000 Feb;127(3):621-30
references: 10631182
references: Development. 2004 Nov;131(21):5327-39
references: 15456730
references: J Neurobiol. 2000 Apr;43(1):1-17
references: 10756062
references: Development. 2003 Dec;130(23):5579-87
references: 14522868
references: Development. 2004 Jun;131(12):2791-801
references: 15142975
references: Development. 2008 Jan;135(2):237-47
references: 18057099
references: Development. 2002 May;129(10):2459-72
references: 11973277
references: J Neuropathol Exp Neurol. 2002 Apr;61(4):297-306
references: 11939585
references: J Dermatol Sci. 2006 May;42(2):111-9
references: 16442268
references: Development. 2001 Nov;128(22):4449-61
references: 11714671
references: BMC Dev Biol. 2002 Jul 02;2:8
references: 12095419
references: Development. 2000 Mar;127(6):1209-20
references: 10683174
references: J Cell Biol. 2003 Jun 9;161(5):911-21
references: 12796477
references: J Neurosci Res. 2008 Jan;86(1):125-35
references: 17722066
references: Trends Neurosci. 1997 Jul;20(7):309-17
references: 9223224
references: Eur J Neurosci. 2004 Sep;20(6):1445-60
references: 15355312
references: Genesis. 2002 Feb;32(2):69-72
references: 11857780
references: Cell. 2001 May 18;105(4):533-45
references: 11371349
references: J Neurosci Res. 2004 Apr 1;76(1):9-19
references: 15048926
references: Stem Cells. 2010 Feb;28(2):297-307
references: 19960516
references: Neuron. 2005 Jan 6;45(1):55-67
references: 15629702
references: Neuron. 2000 Feb;25(2):317-29
references: 10719888
references: Nature. 1998 Nov 26;396(6709):370-3
references: 9845073
references: Mol Cell Neurosci. 2009 Nov;42(3):255-65
references: 19619658
references: Cell. 1995 Sep 22;82(6):969-79
references: 7553857
references: J Neurosci. 2002 Oct 1;22(19):8574-85
references: 12351731
references: Neuron. 2001 Mar;29(3):603-14
references: 11301021
references: Exp Neurol. 2004 Sep;189(1):33-44
references: 15296834
references: Biochem Biophys Res Commun. 2010 Jan 22;391(4):1653-7
references: 20043884
references: Development. 1995 Jun;121(6):1743-54
references: 7600990
references: Cell. 2002 Apr 5;109(1):61-73
references: 11955447
references: Dev Dyn. 2010 Jan;239(1):69-76
references: 19681160
references: Brain Res. 2001 Dec 7;921(1-2):219-25
references: 11720729
references: Development. 2006 Apr;133(7):1219-29
references: 16495310
references: Nature. 2000 Feb 17;403(6771):781-5
references: 10693808
references: Neuron. 2000 Feb;25(2):331-43
references: 10719889
references: Stem Cells. 2007 Jan;25(1):63-8
references: 16973830
references: J Bone Joint Surg Am. 2001;83-A Suppl 1(Pt 1):S31-9
references: 11263663
references: Proc Natl Acad Sci U S A. 1979 Oct;76(10):4913-7
references: 388422
references: Pathology. 2004 Apr;36(2):120-8
references: 15203747
references: Development. 2000 Nov;127(22):4855-66
references: 11044400
references: Dev Biol. 2008 Jan 1;313(1):210-24
references: 18022614
references: J Neurosci. 2008 Aug 13;28(33):8376-82
references: 18701700
references: Neuron. 2005 Jan 6;45(1):41-53
references: 15629701
references: J Neurosci. 2005 Sep 7;25(36):8311-21
references: 16148239
references: Development. 2002 Jul;129(13):3045-54
references: 12070081
references: Dev Dyn. 2010 Jan;239(1):16-33
references: 19544585
references: J Bone Miner Res. 2008 Dec;23(12):2007-17
references: 18684091
references: Dev Biol. 2007 Apr 1;304(1):394-408
references: 17292876
references: EMBO J. 2000 May 2;19(9):1998-2007
references: 10790366
references: Prog Neurobiol. 2002 Aug;67(6):451-67
references: 12385864
references: Development. 2005 Jan;132(1):215-25
references: 15576399
references: Neuron. 2007 Jul 19;55(2):217-30
references: 17640524
references: Genes Cells. 2005 Aug;10(8):777-83
references: 16098141
references: Proc Natl Acad Sci U S A. 2009 Nov 10;106(45):19162-7
references: 19855010
references: Mol Biol Cell. 2010 Sep 15;21(18):3269-77
references: 20668165
references: Mol Cell Neurosci. 2004 Aug;26(4):481-92
references: 15276151
references: J Cell Biol. 2005 May 23;169(4):577-89
references: 15897262
references: Development. 2004 Nov;131(21):5393-403
references: 15469980
references: Dev Biol. 2006 Nov 15;299(2):330-44
references: 17005177
references: Mol Cell Neurosci. 2007 May;35(1):171-82
references: 17391983