Insights Gained From Zebrafish Models for the Ciliopathy Joubert Syndrome.
CRISPR/Cas9
Joubert syndrome
cilia
ciliopathies
morpholino (MO)
retina
zebrafish
Journal
Frontiers in genetics
ISSN: 1664-8021
Titre abrégé: Front Genet
Pays: Switzerland
ID NLM: 101560621
Informations de publication
Date de publication:
2022
2022
Historique:
received:
09
05
2022
accepted:
26
05
2022
entrez:
18
7
2022
pubmed:
19
7
2022
medline:
19
7
2022
Statut:
epublish
Résumé
Cilia are quasi-ubiquitous microtubule-based sensory organelles, which play vital roles in signal transduction during development and cell homeostasis. Dysfunction of cilia leads to a group of Mendelian disorders called ciliopathies, divided into different diagnoses according to clinical phenotype constellation and genetic causes. Joubert syndrome (JBTS) is a prototypical ciliopathy defined by a diagnostic cerebellar and brain stem malformation termed the "Molar Tooth Sign" (MTS), in addition to which patients display variable combinations of typical ciliopathy phenotypes such as retinal dystrophy, fibrocystic renal disease, polydactyly or skeletal dystrophy. Like most ciliopathies, JBTS is genetically highly heterogeneous with ∼40 associated genes. Zebrafish are widely used to model ciliopathies given the high conservation of ciliary genes and the variety of specialized cilia types similar to humans. In this review, we compare different existing JBTS zebrafish models with each other and describe their contributions to our understanding of JBTS pathomechanism. We find that retinal dystrophy, which is the most investigated ciliopathy phenotype in zebrafish ciliopathy models, is caused by distinct mechanisms according to the affected gene. Beyond this, differences in phenotypes in other organs observed between different JBTS-mutant models suggest tissue-specific roles for proteins implicated in JBTS. Unfortunately, the lack of systematic assessment of ciliopathy phenotypes in the mutants described in the literature currently limits the conclusions that can be drawn from these comparisons. In the future, the numerous existing JBTS zebrafish models represent a valuable resource that can be leveraged in order to gain further insights into ciliary function, pathomechanisms underlying ciliopathy phenotypes and to develop treatment strategies using small molecules.
Identifiants
pubmed: 35846153
doi: 10.3389/fgene.2022.939527
pii: 939527
pmc: PMC9280682
doi:
Types de publication
Journal Article
Review
Langues
eng
Pagination
939527Informations de copyright
Copyright © 2022 Rusterholz, Hofmann and Bachmann-Gagescu.
Déclaration de conflit d'intérêts
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
Références
J Pathol. 2019 Aug;248(4):396-408
pubmed: 30924151
Hum Mol Genet. 2015 Mar 1;24(5):1410-9
pubmed: 25361962
Transl Psychiatry. 2019 Jan 15;9(1):4
pubmed: 30664616
Front Pediatr. 2017 Nov 20;5:244
pubmed: 29209597
Cell. 2011 May 13;145(4):513-28
pubmed: 21565611
Development. 2005 Apr;132(8):1907-21
pubmed: 15790966
Hum Mol Genet. 2014 Sep 15;23(R1):R40-6
pubmed: 24651067
Nat Biotechnol. 2011 Aug 05;29(8):699-700
pubmed: 21822242
Brief Funct Genomic Proteomic. 2008 Nov;7(6):454-9
pubmed: 19028802
Science. 2006 Aug 4;313(5787):629-33
pubmed: 16888132
Development. 2004 Aug;131(16):4085-93
pubmed: 15269167
Nat Genet. 2018 Mar;50(3):460-471
pubmed: 29459677
Chem Res Toxicol. 2020 Jan 21;33(1):95-118
pubmed: 31625720
Pediatr Nephrol. 2011 Jul;26(7):1039-56
pubmed: 21210154
Cells. 2016 Jan 29;5(1):
pubmed: 26840332
Dev Biol. 2017 May 15;425(2):176-190
pubmed: 28341548
Cell Rep. 2019 Aug 13;28(7):1907-1922.e6
pubmed: 31412255
Trends Genet. 2017 Mar;33(3):183-196
pubmed: 28174019
Lancet Neurol. 2013 Sep;12(9):894-905
pubmed: 23870701
Front Cell Dev Biol. 2018 Feb 08;6:8
pubmed: 29473038
Nat Cell Biol. 2017 Oct;19(10):1178-1188
pubmed: 28846093
Front Cell Neurosci. 2019 Mar 21;13:81
pubmed: 30949029
Hum Mutat. 2021 Apr;42(4):392-407
pubmed: 33382518
PLoS Genet. 2008 Feb 29;4(2):e1000020
pubmed: 18454195
Sci Rep. 2017 May 9;7(1):1601
pubmed: 28487520
Annu Rev Genomics Hum Genet. 2006;7:125-48
pubmed: 16722803
Development. 2009 Feb;136(4):655-64
pubmed: 19144723
Nat Rev Genet. 2010 Sep;11(9):636-46
pubmed: 20717154
Genes Dev. 2006 May 15;20(10):1365-77
pubmed: 16702409
Am J Hum Genet. 2017 Jul 6;101(1):23-36
pubmed: 28625504
Hum Mol Genet. 2009 Jan 15;18(2):289-303
pubmed: 18971206
Dev Biol. 2008 Jun 1;318(1):162-71
pubmed: 18423594
Curr Biol. 2017 Jan 23;27(2):166-174
pubmed: 28041793
Nat Genet. 2009 Jun;41(6):739-45
pubmed: 19430481
Nat Rev Mol Cell Biol. 2011 Apr;12(4):222-34
pubmed: 21427764
Nat Genet. 2010 Jul;42(7):619-25
pubmed: 20512146
Genes Dev. 1999 Oct 15;13(20):2713-24
pubmed: 10541557
J Clin Invest. 2020 Aug 3;130(8):4423-4439
pubmed: 32453716
Dev Dyn. 2009 Jul;238(7):1744-59
pubmed: 19517571
Genet Med. 2018 Feb;20(2):223-233
pubmed: 28771248
Development. 2011 Aug;138(15):3261-72
pubmed: 21750036
Development. 2008 May;135(10):1735-43
pubmed: 18403413
Neurosci Bull. 2020 Sep;36(9):1023-1034
pubmed: 32812127
Genome Med. 2018 May 30;10(1):40
pubmed: 29843777
PLoS Genet. 2007 May 25;3(5):e78
pubmed: 17530925
J Cell Sci. 2021 Jul 15;134(14):
pubmed: 34155518
PLoS Genet. 2005 Aug;1(2):e19
pubmed: 16121254
EMBO Rep. 2020 Feb 5;21(2):e48290
pubmed: 31885126
Hum Mol Genet. 2013 May 15;22(10):2024-40
pubmed: 23393159
Hum Mol Genet. 2011 Apr 15;20(8):1467-77
pubmed: 21257638
Genetics. 2021 Aug 9;218(4):
pubmed: 34132778
Am J Hum Genet. 2014 Jan 2;94(1):62-72
pubmed: 24360808
J Cell Sci. 2011 Feb 15;124(Pt 4):600-12
pubmed: 21266464
Nature. 2015 Aug 13;524(7564):230-3
pubmed: 26168398
Sci Rep. 2018 Feb 2;8(1):2211
pubmed: 29396404
Zebrafish. 2006;3(2):191-201
pubmed: 18248260
N Engl J Med. 2011 Apr 21;364(16):1533-43
pubmed: 21506742
Cilia. 2012 Jul 02;1(1):10
pubmed: 23352055
Nat Cell Biol. 2010 Apr;12(4):407-12
pubmed: 20305649
Vision Res. 2009 Feb;49(4):479-89
pubmed: 19136023
J Pathol. 2017 Jan;241(2):294-309
pubmed: 27859258
PLoS One. 2019 Apr 10;14(4):e0213960
pubmed: 30970040
Curr Biol. 2018 Aug 6;28(15):2479-2486.e4
pubmed: 30057305
Mol Genet Genomics. 2014 Dec;289(6):1045-60
pubmed: 25092473
Invest Ophthalmol Vis Sci. 2017 Jan 1;58(1):448-460
pubmed: 28118669
Curr Protoc Cell Biol. 2012 Dec;Chapter 4:Unit 4.26
pubmed: 23208547
Results Probl Cell Differ. 2017;60:55-75
pubmed: 28409342
Transl Sci Rare Dis. 2019 Jul 04;4(1-2):25-49
pubmed: 31763177
Microscopy (Oxf). 2019 Apr 1;68(2):99-110
pubmed: 30715429
Proc Natl Acad Sci U S A. 2013 Jul 30;110(31):12697-702
pubmed: 23858445
Dev Cell. 2012 Nov 13;23(5):925-38
pubmed: 23153492
Hum Mol Genet. 2008 Dec 1;17(23):3655-62
pubmed: 18723859
Nat Genet. 2011 Jun;43(6):601-6
pubmed: 21552264
PLoS Genet. 2013;9(12):e1003955
pubmed: 24339784
Curr Opin Genet Dev. 2019 Jun;56:22-33
pubmed: 31260874
Nat Genet. 2008 Apr;40(4):443-8
pubmed: 18327255
Am J Hum Genet. 2014 May 1;94(5):745-54
pubmed: 24746959
J Cell Sci. 2010 Feb 15;123(Pt 4):529-36
pubmed: 20145001
Nature. 2019 Apr;568(7751):193-197
pubmed: 30944477
Sci Rep. 2017 Aug 31;7(1):10222
pubmed: 28860541
Am J Hum Genet. 2011 Dec 9;89(6):713-30
pubmed: 22152675
G3 (Bethesda). 2016 Jul 07;6(7):2225-35
pubmed: 27207957
Curr Opin Cell Biol. 2010 Aug;22(4):541-6
pubmed: 20399632
J Am Soc Nephrol. 2017 Jan;28(1):118-129
pubmed: 27401686
Open Biol. 2013 May 29;3(5):130052
pubmed: 23720541
Dev Biol. 2008 Feb 15;314(2):261-75
pubmed: 18178183
EMBO J. 2011 May 20;30(13):2532-44
pubmed: 21602787
Genome Biol. 2007;8 Suppl 1:S7
pubmed: 18047699
PLoS Biol. 2019 Jul 17;17(7):e3000381
pubmed: 31314751
Science. 2012 Feb 24;335(6071):966-9
pubmed: 22282472
Nat Methods. 2015 Jun;12(6):535-40
pubmed: 25867848
Nat Genet. 2011 Jul 03;43(8):776-84
pubmed: 21725307
J Am Soc Nephrol. 2021 Feb 11;:
pubmed: 33574160
Genet Med. 2009 Jun;11(6):386-402
pubmed: 19421068
Front Cell Dev Biol. 2018 Sep 19;6:110
pubmed: 30283779
Cell Mol Life Sci. 2012 Mar;69(6):993-1009
pubmed: 21959375
Am J Hum Genet. 2008 Aug;83(2):170-9
pubmed: 18674751
Hum Mol Genet. 2015 May 1;24(9):2594-603
pubmed: 25616960
Nat Genet. 2012 Jan 15;44(2):193-9
pubmed: 22246503
PLoS Genet. 2017 Oct 19;13(10):e1007000
pubmed: 29049395
Nat Rev Genet. 2010 May;11(5):331-44
pubmed: 20395968
Vision Res. 2012 Dec 15;75:98-107
pubmed: 23022135
Prog Mol Biol Transl Sci. 2011;100:287-330
pubmed: 21377629
Hum Mol Genet. 2015 Jan 1;24(1):230-42
pubmed: 25168386
Front Neuroanat. 2016 May 02;10:49
pubmed: 27199681
Sci Rep. 2021 Jun 1;11(1):11432
pubmed: 34075074
Am J Hum Genet. 2011 Jul 15;89(1):94-110
pubmed: 21763481
Development. 2009 Dec;136(23):4033-42
pubmed: 19906870
Nat Genet. 2002 Jun;31(2):135-40
pubmed: 12006978
J Cell Biol. 2012 Sep 3;198(5):927-40
pubmed: 22927466
PLoS Genet. 2015 Oct 20;11(10):e1005575
pubmed: 26485645
Curr Biol. 2020 Jun 22;30(12):2353-2362.e3
pubmed: 32386529
Development. 2011 Nov;138(22):4969-78
pubmed: 22028029
Hum Mol Genet. 2017 Jul 1;26(13):2480-2492
pubmed: 28444310
Am J Med Genet A. 2020 Jan;182(1):229-249
pubmed: 31710777
Development. 2005 Feb;132(4):625-34
pubmed: 15647323
J Biol Chem. 2011 Aug 12;286(32):28276-86
pubmed: 21685394
Front Pediatr. 2018 Jun 28;6:183
pubmed: 30003073
Dev Dyn. 2009 Sep;238(9):2115-38
pubmed: 19582864
Nature. 2009 May 7;459(7243):98-102
pubmed: 19305393
Kidney Int. 2008 May;73(10):1120-7
pubmed: 18322540
Methods Cell Biol. 2011;101:39-74
pubmed: 21550439
Nat Genet. 2000 Oct;26(2):216-20
pubmed: 11017081
Hum Mutat. 2014 Jan;35(1):137-46
pubmed: 24166846
Adv Exp Med Biol. 2007;607:130-40
pubmed: 17977465
Science. 2022 Jun 17;376(6599):eabh3104
pubmed: 35549308
Am J Hum Genet. 2008 Nov;83(5):559-71
pubmed: 18950740
Invest Ophthalmol Vis Sci. 2016 Aug 1;57(10):4517-26
pubmed: 27571019
Invest Ophthalmol Vis Sci. 2020 Jul 1;61(8):24
pubmed: 32687549
PLoS Genet. 2017 Dec 27;13(12):e1007150
pubmed: 29281629
J Med Genet. 2015 Aug;52(8):514-22
pubmed: 26092869
Genetics. 2005 May;170(1):245-61
pubmed: 15716491
Eur J Hum Genet. 2015 May;23(5):621-7
pubmed: 25138100
Sci Rep. 2017 Nov 14;7(1):15585
pubmed: 29138412
Hum Mol Genet. 2012 Mar 15;21(6):1272-86
pubmed: 22121117
Nat Genet. 2006 Jun;38(6):674-81
pubmed: 16682973
J Cell Biol. 2014 Jan 20;204(2):215-29
pubmed: 24421332
Hum Genet. 2016 Aug;135(8):919-921
pubmed: 27245168
Nature. 2013 Apr 25;496(7446):498-503
pubmed: 23594743
Cold Spring Harb Perspect Biol. 2017 May 1;9(5):
pubmed: 27881449
Hum Mol Genet. 2011 Oct 15;20(20):4041-55
pubmed: 21816947
Curr Opin Genet Dev. 2009 Aug;19(4):396-403
pubmed: 19608405
J Clin Invest. 2012 Jul;122(7):2337-43
pubmed: 22751109
Hum Mol Genet. 2011 Aug 15;20(16):3119-28
pubmed: 21596840
Cell. 2021 May 27;184(11):2911-2926.e18
pubmed: 33932338
Arterioscler Thromb Vasc Biol. 2018 Dec;38(12):2806-2818
pubmed: 30571172
J Cell Biol. 2011 Mar 21;192(6):1023-41
pubmed: 21422230
Annu Rev Cell Dev Biol. 2010;26:59-87
pubmed: 19575670
Am J Hum Genet. 2013 Nov 7;93(5):915-25
pubmed: 24140113
Hum Mutat. 2009 Nov;30(11):1574-82
pubmed: 19777577
Cilia. 2018 Mar 15;7:2
pubmed: 29568513