Discovery, Diagnosis, and Etiology of Craniofacial Ciliopathies

Overview

Journal Cold Spring Harb Perspect Biol

Specialties Biology
Molecular Biology

Date 2017 Feb 19

PMID 28213462

Citations 26

Authors

Elizabeth N Schock

Samantha A Brugmann

Affiliations

Soon will be listed here.

Abstract

Seventy-five percent of congenital disorders present with some form of craniofacial malformation. The frequency and severity of these malformations makes understanding the etiological basis crucial for diagnosis and treatment. A significant link between craniofacial malformations and primary cilia arose several years ago with the determination that ∼30% of ciliopathies could be primarily defined by their craniofacial phenotype. The link between the cilium and the face has proven significant, as several new "craniofacial ciliopathies" have recently been diagnosed. Herein, we reevaluate public disease databases, report several new craniofacial ciliopathies, and propose several "predicted" craniofacial ciliopathies. Furthermore, we discuss why the craniofacial complex is so sensitive to ciliopathic dysfunction, addressing tissue-specific functions of the cilium as well as its role in signal transduction relevant to craniofacial development. As a whole, these analyses suggest a characteristic facial phenotype associated with craniofacial ciliopathies that can perhaps be used for rapid discovery and diagnosis of similar disorders in the future.

Citing Articles

Transcriptome-wide association identifies as a regulator of mitophagy in non-syndromic cleft lip with or without palate.

Lou S, Zhu G, Xing C, Hao S, Lin J, Xu J Imeta. 2025; 3(6):e262.

PMID: 39742305 PMC: 11683466. DOI: 10.1002/imt2.262.

Actin cytoskeletal regulation of ciliogenesis in development and disease.

Hufft-Martinez B, Wang H, Saadi I, Tran P Dev Dyn. 2024; 253(12):1076-1093.

PMID: 38958410 PMC: 11611694. DOI: 10.1002/dvdy.724.

Molecular and structural perspectives on protein trafficking to the primary cilium membrane.

Palicharla V, Mukhopadhyay S Biochem Soc Trans. 2024; 52(3):1473-1487.

PMID: 38864436 PMC: 11346432. DOI: 10.1042/BST20231403.

The ciliary protein C2cd3 is required for mandibular musculoskeletal tissue patterning.

Brooks E, Han S, Bonatto Paese C, Lewis A, Aarnio-Peterson M, Brugmann S Differentiation. 2024; 138:100782.

PMID: 38810379 PMC: 11227401. DOI: 10.1016/j.diff.2024.100782.

Characteristic craniofacial defects associated with a novel USP9X truncation mutation.

Nagata N, Kurosaka H, Higashi K, Yamaguchi M, Yamamoto S, Inubushi T Hum Genome Var. 2024; 11(1):21.

PMID: 38755172 PMC: 11099082. DOI: 10.1038/s41439-024-00277-w.

References

Dasgupta R, Fuchs E . Multiple roles for activated LEF/TCF transcription complexes during hair follicle development and differentiation. Development. 1999; 126(20):4557-68. DOI: 10.1242/dev.126.20.4557. View

Hu D, Helms J . The role of sonic hedgehog in normal and abnormal craniofacial morphogenesis. Development. 1999; 126(21):4873-84. DOI: 10.1242/dev.126.21.4873. View

Rice D, Aberg T, Chan Y, Tang Z, Kettunen P, Pakarinen L . Integration of FGF and TWIST in calvarial bone and suture development. Development. 2000; 127(9):1845-55. DOI: 10.1242/dev.127.9.1845. View

Graham A, Smith A . Patterning the pharyngeal arches. Bioessays. 2001; 23(1):54-61. DOI: 10.1002/1521-1878(200101)23:1<54::AID-BIES1007>3.0.CO;2-5. View

Juriloff D, Harris M, Brown C . Unravelling the complex genetics of cleft lip in the mouse model. Mamm Genome. 2001; 12(6):426-35. DOI: 10.1007/s003350010284. View

Couly G, Creuzet S, Bennaceur S, Vincent C, Le Douarin N . Interactions between Hox-negative cephalic neural crest cells and the foregut endoderm in patterning the facial skeleton in the vertebrate head. Development. 2002; 129(4):1061-73. DOI: 10.1242/dev.129.4.1061. View

Maretto S, Cordenonsi M, Dupont S, Braghetta P, Broccoli V, Hassan A . Mapping Wnt/beta-catenin signaling during mouse development and in colorectal tumors. Proc Natl Acad Sci U S A. 2003; 100(6):3299-304. PMC: 152286. DOI: 10.1073/pnas.0434590100. View

Watanabe D, Saijoh Y, Nonaka S, Sasaki G, Ikawa Y, Yokoyama T . The left-right determinant Inversin is a component of node monocilia and other 9+0 cilia. Development. 2003; 130(9):1725-34. DOI: 10.1242/dev.00407. View

Graham A . Development of the pharyngeal arches. Am J Med Genet A. 2003; 119A(3):251-6. DOI: 10.1002/ajmg.a.10980. View

10.

Otto E, Schermer B, Obara T, OToole J, Hiller K, Mueller A . Mutations in INVS encoding inversin cause nephronophthisis type 2, linking renal cystic disease to the function of primary cilia and left-right axis determination. Nat Genet. 2003; 34(4):413-20. PMC: 3732175. DOI: 10.1038/ng1217. View

11.

Roessler E, Du Y, Mullor J, Casas E, Allen W, Gillessen-Kaesbach G . Loss-of-function mutations in the human GLI2 gene are associated with pituitary anomalies and holoprosencephaly-like features. Proc Natl Acad Sci U S A. 2003; 100(23):13424-9. PMC: 263830. DOI: 10.1073/pnas.2235734100. View

12.

Walshe J, Mason I . Fgf signalling is required for formation of cartilage in the head. Dev Biol. 2003; 264(2):522-36. DOI: 10.1016/j.ydbio.2003.08.010. View

13.

Cano D, Murcia N, Pazour G, Hebrok M . Orpk mouse model of polycystic kidney disease reveals essential role of primary cilia in pancreatic tissue organization. Development. 2004; 131(14):3457-67. DOI: 10.1242/dev.01189. View

14.

Abzhanov A, Protas M, Grant B, Grant P, Tabin C . Bmp4 and morphological variation of beaks in Darwin's finches. Science. 2004; 305(5689):1462-5. DOI: 10.1126/science.1098095. View

15.

Le Douarin N, Creuzet S, Couly G, Dupin E . Neural crest cell plasticity and its limits. Development. 2004; 131(19):4637-50. DOI: 10.1242/dev.01350. View

16.

Buxton P, Davey M, Paton I, Morrice D, Francis-West P, Burt D . Craniofacial development in the talpid3 chicken mutant. Differentiation. 2004; 72(7):348-62. DOI: 10.1111/j.1432-0436.2004.07207006.x. View

17.

Song Y, Hui J, Fu K, Richman J . Control of retinoic acid synthesis and FGF expression in the nasal pit is required to pattern the craniofacial skeleton. Dev Biol. 2004; 276(2):313-29. DOI: 10.1016/j.ydbio.2004.08.035. View

18.

Juriloff D, Harris M, Dewell S, Brown C, Mager D, Gagnier L . Investigations of the genomic region that contains the clf1 mutation, a causal gene in multifactorial cleft lip and palate in mice. Birth Defects Res A Clin Mol Teratol. 2005; 73(2):103-13. DOI: 10.1002/bdra.20106. View

19.

Simons M, Gloy J, Ganner A, Bullerkotte A, Bashkurov M, Kronig C . Inversin, the gene product mutated in nephronophthisis type II, functions as a molecular switch between Wnt signaling pathways. Nat Genet. 2005; 37(5):537-43. PMC: 3733333. DOI: 10.1038/ng1552. View

20.

Schmidt C, Patel K . Wnts and the neural crest. Anat Embryol (Berl). 2005; 209(5):349-55. DOI: 10.1007/s00429-005-0459-9. View