Expression Patterns of Ciliopathy Genes ARL3 and CEP120 Reveal Roles in Multisystem Development

Overview

Journal BMC Dev Biol

Publisher Biomed Central

Specialties Biology
Reproductive Medicine

Date 2020 Dec 10

PMID 33297941

Citations 4

Authors

L Powell

M Barroso-Gil

G J Clowry

L A Devlin

E Molinari

S A Ramsbottom

C G Miles

J A Sayer

Affiliations

Soon will be listed here.

Abstract

Background: Joubert syndrome and related disorders (JSRD) and Jeune syndrome are multisystem ciliopathy disorders with overlapping phenotypes. There are a growing number of genetic causes for these rare syndromes, including the recently described genes ARL3 and CEP120.

Methods: We sought to explore the developmental expression patterns of ARL3 and CEP120 in humans to gain additional understanding of these genetic conditions. We used an RNA in situ detection technique called RNAscope to characterise ARL3 and CEP120 expression patterns in human embryos and foetuses in collaboration with the MRC-Wellcome Trust Human Developmental Biology Resource.

Results: Both ARL3 and CEP120 are expressed in early human brain development, including the cerebellum and in the developing retina and kidney, consistent with the clinical phenotypes seen with pathogenic variants in these genes.

Conclusions: This study provides insights into the potential pathogenesis of JSRD by uncovering the spatial expression of two JSRD-causative genes during normal human development.

Citing Articles

The temporal progression of retinal degeneration and early-stage idebenone treatment in the Pde6b mouse model of retinal dystrophy.

Zhang L, Liu W, Wang H, Qiang W, Wang R, Cui Z Sci Rep. 2024; 14(1):2019.

PMID: 38263197 PMC: 10805728. DOI: 10.1038/s41598-024-52391-y.

Genotype-phenotype correlates in Joubert syndrome: A review.

Gana S, Serpieri V, Valente E Am J Med Genet C Semin Med Genet. 2022; 190(1):72-88.

PMID: 35238134 PMC: 9314610. DOI: 10.1002/ajmg.c.31963.

CEP120-mediated KIAA0753 recruitment onto centrioles is required for timely neuronal differentiation and germinal zone exit in the developing cerebellum.

Chang C, Chen T, Lu I, Li R, Tsai J, Lin P Genes Dev. 2021; 35(21-22):1445-1460.

PMID: 34711653 PMC: 8559671. DOI: 10.1101/gad.348636.121.

Fetal ciliopathies: a retrospective observational single-center study.

Simonini C, Floeck A, Strizek B, Mueller A, Gembruch U, Geipel A Arch Gynecol Obstet. 2021; 306(1):71-83.

PMID: 34596737 PMC: 9300526. DOI: 10.1007/s00404-021-06265-7.

References

Taverna E, Huttner W . Neural progenitor nuclei IN motion. Neuron. 2010; 67(6):906-14. DOI: 10.1016/j.neuron.2010.08.027. View

Schrick J, Vogel P, Abuin A, Hampton B, Rice D . ADP-ribosylation factor-like 3 is involved in kidney and photoreceptor development. Am J Pathol. 2006; 168(4):1288-98. PMC: 1606550. DOI: 10.2353/ajpath.2006.050941. View

Wang H, Wang M, Su N, Wang L, Wu X, Bui S . RNAscope for in situ detection of transcriptionally active human papillomavirus in head and neck squamous cell carcinoma. J Vis Exp. 2014; (85). PMC: 4145807. DOI: 10.3791/51426. View

Hoon M, Okawa H, Santina L, Wong R . Functional architecture of the retina: development and disease. Prog Retin Eye Res. 2014; 42:44-84. PMC: 4134977. DOI: 10.1016/j.preteyeres.2014.06.003. View

Roosing S, Romani M, Isrie M, Rosti R, Micalizzi A, Musaev D . Mutations in CEP120 cause Joubert syndrome as well as complex ciliopathy phenotypes. J Med Genet. 2016; 53(9):608-15. PMC: 5013089. DOI: 10.1136/jmedgenet-2016-103832. View

Sotelo C . Molecular layer interneurons of the cerebellum: developmental and morphological aspects. Cerebellum. 2015; 14(5):534-56. DOI: 10.1007/s12311-015-0648-x. View

Tucker R, Pardee A, Fujiwara K . Centriole ciliation is related to quiescence and DNA synthesis in 3T3 cells. Cell. 1979; 17(3):527-35. DOI: 10.1016/0092-8674(79)90261-7. View

Xie Z, Moy L, Sanada K, Zhou Y, Buchman J, Tsai L . Cep120 and TACCs control interkinetic nuclear migration and the neural progenitor pool. Neuron. 2007; 56(1):79-93. PMC: 2642594. DOI: 10.1016/j.neuron.2007.08.026. View

Krames E . The role of the dorsal root ganglion in the development of neuropathic pain. Pain Med. 2014; 15(10):1669-85. DOI: 10.1111/pme.12413. View

10.

Paprocka J, Jamroz E . [Joubert syndrome and related disorders]. Neurol Neurochir Pol. 2012; 46(4):379-83. DOI: 10.5114/ninp.2012.30457. View

11.

Shaheen R, Schmidts M, Faqeih E, Hashem A, Lausch E, Holder I . A founder CEP120 mutation in Jeune asphyxiating thoracic dystrophy expands the role of centriolar proteins in skeletal ciliopathies. Hum Mol Genet. 2014; 24(5):1410-9. PMC: 4321448. DOI: 10.1093/hmg/ddu555. View

12.

Malicdan M, Vilboux T, Stephen J, Maglic D, Mian L, Konzman D . Mutations in human homologue of chicken talpid3 gene (KIAA0586) cause a hybrid ciliopathy with overlapping features of Jeune and Joubert syndromes. J Med Genet. 2015; 52(12):830-9. PMC: 5517294. DOI: 10.1136/jmedgenet-2015-103316. View

13.

Gotthardt K, Lokaj M, Koerner C, Falk N, Giessl A, Wittinghofer A . A G-protein activation cascade from Arl13B to Arl3 and implications for ciliary targeting of lipidated proteins. Elife. 2015; 4. PMC: 4868535. DOI: 10.7554/eLife.11859. View

14.

Tsai J, Hsu W, Liu J, Chang C, Tang T . CEP120 interacts with C2CD3 and Talpid3 and is required for centriole appendage assembly and ciliogenesis. Sci Rep. 2019; 9(1):6037. PMC: 6465297. DOI: 10.1038/s41598-019-42577-0. View

15.

Berbari N, OConnor A, Haycraft C, Yoder B . The primary cilium as a complex signaling center. Curr Biol. 2009; 19(13):R526-35. PMC: 2814769. DOI: 10.1016/j.cub.2009.05.025. View

16.

Alkanderi S, Molinari E, Shaheen R, ElMaghloob Y, Stephen L, Sammut V . ARL3 Mutations Cause Joubert Syndrome by Disrupting Ciliary Protein Composition. Am J Hum Genet. 2018; 103(4):612-620. PMC: 6174286. DOI: 10.1016/j.ajhg.2018.08.015. View

17.

Hatten M, Heintz N . Mechanisms of neural patterning and specification in the developing cerebellum. Annu Rev Neurosci. 1995; 18:385-408. DOI: 10.1146/annurev.ne.18.030195.002125. View

18.

Blacque O, Perens E, Boroevich K, Inglis P, Li C, Warner A . Functional genomics of the cilium, a sensory organelle. Curr Biol. 2005; 15(10):935-41. DOI: 10.1016/j.cub.2005.04.059. View

19.

Li Y, Wei Q, Zhang Y, Ling K, Hu J . The small GTPases ARL-13 and ARL-3 coordinate intraflagellar transport and ciliogenesis. J Cell Biol. 2010; 189(6):1039-51. PMC: 2886347. DOI: 10.1083/jcb.200912001. View

20.

Kahn R, Der C, Bokoch G . The ras superfamily of GTP-binding proteins: guidelines on nomenclature. FASEB J. 1992; 6(8):2512-3. DOI: 10.1096/fasebj.6.8.1592203. View