Thrombospondin-1 Mediates Axon Regeneration in Retinal Ganglion Cells.
Animals
Apoptosis
Axons
/ metabolism
Cell Line
Female
Gene Expression Profiling
Genes, Reporter
Insulin-Like Growth Factor I
/ deficiency
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
Mice, Transgenic
Nerve Crush
Nerve Regeneration
/ physiology
Optic Nerve Injuries
/ genetics
Recombinant Fusion Proteins
/ biosynthesis
Retinal Ganglion Cells
/ physiology
Rod Opsins
/ deficiency
T-Box Domain Proteins
/ deficiency
Thrombospondin 1
/ biosynthesis
Transcription, Genetic
axon growth
axon injury
axon regeneration
extracellular matrix protein
ipRGCs
melanopsin
retina
retinal ganglion cells
syndecan
thrombospondin
Journal
Neuron
ISSN: 1097-4199
Titre abrégé: Neuron
Pays: United States
ID NLM: 8809320
Informations de publication
Date de publication:
21 08 2019
21 08 2019
Historique:
received:
05
10
2018
revised:
11
02
2019
accepted:
28
05
2019
pubmed:
1
7
2019
medline:
29
10
2019
entrez:
1
7
2019
Statut:
ppublish
Résumé
Neuronal subtypes show diverse injury responses, but the molecular underpinnings remain elusive. Using transgenic mice that allow reliable visualization of axonal fate, we demonstrate that intrinsically photosensitive retinal ganglion cells (ipRGCs) are both resilient to cell death and highly regenerative. Using RNA sequencing (RNA-seq), we show genes that are differentially expressed in ipRGCs and that associate with their survival and axon regeneration. Strikingly, thrombospondin-1 (Thbs1) ranked as the most differentially expressed gene, along with the well-documented injury-response genes Atf3 and Jun. THBS1 knockdown in RGCs eliminated axon regeneration. Conversely, RGC overexpression of THBS1 enhanced regeneration in both ipRGCs and non-ipRGCs, an effect that was dependent on syndecan-1, a known THBS1-binding protein. All structural domains of the THBS1 were not equally effective; the trimerization and C-terminal domains promoted regeneration, while the THBS type-1 repeats were dispensable. Our results identify cell-type-specific induction of Thbs1 as a novel gene conferring high regenerative capacity.
Identifiants
pubmed: 31255486
pii: S0896-6273(19)30497-0
doi: 10.1016/j.neuron.2019.05.044
pmc: PMC6706310
mid: NIHMS1530977
pii:
doi:
Substances chimiques
Eomes protein, mouse
0
Recombinant Fusion Proteins
0
Rod Opsins
0
T-Box Domain Proteins
0
Thrombospondin 1
0
insulin-like growth factor-1, mouse
0
melanopsin
0
Insulin-Like Growth Factor I
67763-96-6
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
642-657.e7Subventions
Organisme : NEI NIH HHS
ID : F30 EY025527
Pays : United States
Organisme : NIDCD NIH HHS
ID : R01 DC017303
Pays : United States
Organisme : NIDCD NIH HHS
ID : R01 DC006308
Pays : United States
Organisme : NICHD NIH HHS
ID : R01 HD057632
Pays : United States
Organisme : NEI NIH HHS
ID : U01 EY027257
Pays : United States
Organisme : NIDCD NIH HHS
ID : R01 DC014420
Pays : United States
Organisme : NEI NIH HHS
ID : R01 EY022961
Pays : United States
Informations de copyright
Copyright © 2019 Elsevier Inc. All rights reserved.
Références
J Neurotrauma. 2011 Dec;28(12):2475-83
pubmed: 21861632
J Cell Biol. 2001 Mar 19;152(6):1169-82
pubmed: 11257118
Proc Natl Acad Sci U S A. 2016 Feb 16;113(7):1937-42
pubmed: 26831088
Trends Neurosci. 2014 Oct;37(10):583-93
pubmed: 25218468
Blood Adv. 2017 Nov 16;1(25):2307-2319
pubmed: 29296880
Neuroscience. 2015 Aug 6;300:338-50
pubmed: 26002314
eNeuro. 2017 Aug 29;4(4):
pubmed: 28856242
Rev Physiol Biochem Pharmacol. 2012;162:59-90
pubmed: 22160822
J Neurophysiol. 2008 Jul;100(1):371-84
pubmed: 18480363
Trends Neurosci. 2008 May;31(5):215-20
pubmed: 18395807
Cell. 2015 May 21;161(5):1202-1214
pubmed: 26000488
PLoS One. 2014 Mar 26;9(3):e93274
pubmed: 24671191
Invest Ophthalmol Vis Sci. 2015 Jul;56(8):4309-23
pubmed: 26176868
Sci Rep. 2018 Feb 1;8(1):2054
pubmed: 29391597
J Neurosci. 2014 Sep 24;34(39):13083-95
pubmed: 25253855
Neuron. 2016 Mar 2;89(5):956-70
pubmed: 26898779
PLoS One. 2009 Oct 14;4(10):e7467
pubmed: 19826483
Int J Biochem Cell Biol. 2004 Jun;36(6):961-8
pubmed: 15094109
Vision Res. 2004 Oct;44(23):2667-74
pubmed: 15358062
Nat Neurosci. 2012 Jan 22;15(3):487-95, S1-2
pubmed: 22267162
J Neurosci. 1993 May;13(5):2105-17
pubmed: 8478691
Science. 2009 Oct 9;326(5950):298-301
pubmed: 19815778
Cell. 2005 Feb 11;120(3):421-33
pubmed: 15707899
Invest Ophthalmol Vis Sci. 2006 Jul;47(7):2951-8
pubmed: 16799038
Nature. 2011 Nov 06;480(7377):372-5
pubmed: 22056987
J Neurosci. 2004 Dec 1;24(48):10806-15
pubmed: 15574731
Proc Natl Acad Sci U S A. 2012 Jun 5;109(23):9149-54
pubmed: 22615390
Chronobiol Int. 2006;23(1-2):159-66
pubmed: 16687290
Neuron. 2012 Feb 9;73(3):445-52
pubmed: 22325198
Matrix Biol. 2014 Jul;37:83-91
pubmed: 24476925
Cell. 2009 Oct 16;139(2):380-92
pubmed: 19818485
Neuron. 1991 Mar;6(3):345-58
pubmed: 1705807
Nat Neurosci. 2016 Aug;19(8):1073-84
pubmed: 27399843
Science. 2008 Nov 7;322(5903):963-6
pubmed: 18988856
J Neurosci. 2004 Oct 6;24(40):8726-40
pubmed: 15470139
Neuron. 2015 Mar 18;85(6):1244-56
pubmed: 25754821
Neuron. 1991 Aug;7(2):231-7
pubmed: 1873028
J Cell Sci. 2002 Jun 1;115(Pt 11):2357-66
pubmed: 12006620
Cell Death Dis. 2013 Sep 19;4:e805
pubmed: 24052073
Biol Rev Camb Philos Soc. 2018 Aug;93(3):1339-1362
pubmed: 29446228
Dev Biol. 1992 Apr;150(2):256-65
pubmed: 1551474
Cell Rep. 2014 Jul 10;8(1):272-83
pubmed: 25001284
Cell. 2012 Jun 8;149(6):1257-68
pubmed: 22682248
Annu Rev Neurosci. 2015 Jul 8;38:221-46
pubmed: 25897874
Brain. 2010 Aug;133(Pt 8):2426-38
pubmed: 20659957
J Neurosci Res. 1994 Jun 1;38(2):221-33
pubmed: 8078107
Nature. 2011 Jul 17;476(7358):92-5
pubmed: 21765429
J Neurosci. 2011 Nov 9;31(45):16094-101
pubmed: 22072661
Cell Mol Life Sci. 2013 Mar;70(5):935-50
pubmed: 23052218
Mol Cell Neurosci. 2018 Oct;92:114-127
pubmed: 30077771
Dev Dyn. 1992 Apr;193(4):346-58
pubmed: 1380845