Fuz Mutant Mice Reveal Shared Mechanisms between Ciliopathies and FGF-Related Syndromes

Jacqueline M Tabler; William B Barrell; Heather L Szabo-Rogers; Christopher Healy; Yvonne Yeung; Elisa Gomez Perdiguero; Christian Schulz; Basil Z Yannakoudakis; Aida Mesbahi; Bogdan Wlodarczyk; Frederic Geissmann; Richard H Finnell; John B Wallingford; Karen J Liu

doi:10.1016/j.devcel.2013.05.021

Fuz Mutant Mice Reveal Shared Mechanisms between Ciliopathies and FGF-Related Syndromes

Jacqueline M Tabler, William B Barrell, Heather L Szabo-Rogers, Christopher Healy, Yvonne Yeung, Elisa Gomez Perdiguero, Christian Schulz, Basil Z Yannakoudakis, Aida Mesbahi, Bogdan Wlodarczyk, Frederic Geissmann, Richard H Finnell, John B Wallingford, Karen J Liu

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Abstract

Ciliopathies are a broad class of human disorders with craniofacial dysmorphology as a common feature. Among these is high arched palate, a condition that affects speech and quality of life. Using the ciliopathic Fuz mutant mouse, we find that high arched palate does not, as commonly suggested, arise from midface hypoplasia. Rather, increased neural crest expands the maxillary primordia. In Fuz mutants, this phenotype stems from dysregulated Gli processing, which in turn results in excessive craniofacial Fgf8 gene expression. Accordingly, genetic reduction of Fgf8 ameliorates the maxillary phenotypes. Similar phenotypes result from mutation of oral-facial-digital syndrome 1 (Ofd1), suggesting that aberrant transcription of Fgf8 is a common feature of ciliopathies. High arched palate is also a prevalent feature of fibroblast growth factor (FGF) hyperactivation syndromes. Thus, our findings elucidate the etiology for a common craniofacial anomaly and identify links between two classes of human disease: FGF-hyperactivation syndromes and ciliopathies.

Original language	English
Pages (from-to)	623-635
Number of pages	13
Journal	Developmental Cell
Volume	25
Issue number	6
DOIs	https://doi.org/10.1016/j.devcel.2013.05.021
Publication status	Published - 24 Jun 2013

Keywords

Animals
Bardet-Biedl Syndrome
Cell Movement
Ciliary Motility Disorders
Craniofacial Abnormalities
Disease Models, Animal
Fibroblast Growth Factor 8
Intracellular Signaling Peptides and Proteins
Kruppel-Like Transcription Factors
Maxilla
Mice
Mice, Mutant Strains
Neural Crest
Orofaciodigital Syndromes
Palate
Phenotype

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.devcel.2013.05.021

Fuz mutant mice reveal shared mechanisms between ciliopathies and FGF related syndromesFinal published version, 4.27 MB

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Tabler, J. M., Barrell, W. B., Szabo-Rogers, H. L., Healy, C., Yeung, Y., Perdiguero, E. G., Schulz, C., Yannakoudakis, B. Z., Mesbahi, A., Wlodarczyk, B., Geissmann, F., Finnell, R. H., Wallingford, J. B., & Liu, K. J. (2013). Fuz Mutant Mice Reveal Shared Mechanisms between Ciliopathies and FGF-Related Syndromes. Developmental Cell, 25(6), 623-635. https://doi.org/10.1016/j.devcel.2013.05.021

@article{d097f87d283146ea801f106755a42c0e,

title = "Fuz Mutant Mice Reveal Shared Mechanisms between Ciliopathies and FGF-Related Syndromes",

abstract = "Ciliopathies are a broad class of human disorders with craniofacial dysmorphology as a common feature. Among these is high arched palate, a condition that affects speech and quality of life. Using the ciliopathic Fuz mutant mouse, we find that high arched palate does not, as commonly suggested, arise from midface hypoplasia. Rather, increased neural crest expands the maxillary primordia. In Fuz mutants, this phenotype stems from dysregulated Gli processing, which in turn results in excessive craniofacial Fgf8 gene expression. Accordingly, genetic reduction of Fgf8 ameliorates the maxillary phenotypes. Similar phenotypes result from mutation of oral-facial-digital syndrome 1 (Ofd1), suggesting that aberrant transcription of Fgf8 is a common feature of ciliopathies. High arched palate is also a prevalent feature of fibroblast growth factor (FGF) hyperactivation syndromes. Thus, our findings elucidate the etiology for a common craniofacial anomaly and identify links between two classes of human disease: FGF-hyperactivation syndromes and ciliopathies.",

keywords = "Animals, Bardet-Biedl Syndrome, Cell Movement, Ciliary Motility Disorders, Craniofacial Abnormalities, Disease Models, Animal, Fibroblast Growth Factor 8, Intracellular Signaling Peptides and Proteins, Kruppel-Like Transcription Factors, Maxilla, Mice, Mice, Mutant Strains, Neural Crest, Orofaciodigital Syndromes, Palate, Phenotype",

author = "Tabler, {Jacqueline M} and Barrell, {William B} and Szabo-Rogers, {Heather L} and Christopher Healy and Yvonne Yeung and Perdiguero, {Elisa Gomez} and Christian Schulz and Yannakoudakis, {Basil Z} and Aida Mesbahi and Bogdan Wlodarczyk and Frederic Geissmann and Finnell, {Richard H} and Wallingford, {John B} and Liu, {Karen J}",

year = "2013",

month = jun,

day = "24",

doi = "10.1016/j.devcel.2013.05.021",

language = "English",

volume = "25",

pages = "623--635",

journal = "Developmental Cell",

issn = "1534-5807",

publisher = "Cell Press",

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Tabler, JM , Barrell, WB, Szabo-Rogers, HL, Healy, C, Yeung, Y, Perdiguero, EG , Schulz, C , Yannakoudakis, BZ , Mesbahi, A, Wlodarczyk, B, Geissmann, F, Finnell, RH, Wallingford, JB & Liu, KJ 2013, 'Fuz Mutant Mice Reveal Shared Mechanisms between Ciliopathies and FGF-Related Syndromes', Developmental Cell, vol. 25, no. 6, pp. 623-635. https://doi.org/10.1016/j.devcel.2013.05.021

TY - JOUR

T1 - Fuz Mutant Mice Reveal Shared Mechanisms between Ciliopathies and FGF-Related Syndromes

AU - Tabler, Jacqueline M

AU - Barrell, William B

AU - Szabo-Rogers, Heather L

AU - Healy, Christopher

AU - Yeung, Yvonne

AU - Perdiguero, Elisa Gomez

AU - Schulz, Christian

AU - Yannakoudakis, Basil Z

AU - Mesbahi, Aida

AU - Wlodarczyk, Bogdan

AU - Geissmann, Frederic

AU - Finnell, Richard H

AU - Wallingford, John B

AU - Liu, Karen J

PY - 2013/6/24

Y1 - 2013/6/24

N2 - Ciliopathies are a broad class of human disorders with craniofacial dysmorphology as a common feature. Among these is high arched palate, a condition that affects speech and quality of life. Using the ciliopathic Fuz mutant mouse, we find that high arched palate does not, as commonly suggested, arise from midface hypoplasia. Rather, increased neural crest expands the maxillary primordia. In Fuz mutants, this phenotype stems from dysregulated Gli processing, which in turn results in excessive craniofacial Fgf8 gene expression. Accordingly, genetic reduction of Fgf8 ameliorates the maxillary phenotypes. Similar phenotypes result from mutation of oral-facial-digital syndrome 1 (Ofd1), suggesting that aberrant transcription of Fgf8 is a common feature of ciliopathies. High arched palate is also a prevalent feature of fibroblast growth factor (FGF) hyperactivation syndromes. Thus, our findings elucidate the etiology for a common craniofacial anomaly and identify links between two classes of human disease: FGF-hyperactivation syndromes and ciliopathies.

AB - Ciliopathies are a broad class of human disorders with craniofacial dysmorphology as a common feature. Among these is high arched palate, a condition that affects speech and quality of life. Using the ciliopathic Fuz mutant mouse, we find that high arched palate does not, as commonly suggested, arise from midface hypoplasia. Rather, increased neural crest expands the maxillary primordia. In Fuz mutants, this phenotype stems from dysregulated Gli processing, which in turn results in excessive craniofacial Fgf8 gene expression. Accordingly, genetic reduction of Fgf8 ameliorates the maxillary phenotypes. Similar phenotypes result from mutation of oral-facial-digital syndrome 1 (Ofd1), suggesting that aberrant transcription of Fgf8 is a common feature of ciliopathies. High arched palate is also a prevalent feature of fibroblast growth factor (FGF) hyperactivation syndromes. Thus, our findings elucidate the etiology for a common craniofacial anomaly and identify links between two classes of human disease: FGF-hyperactivation syndromes and ciliopathies.

KW - Animals

KW - Bardet-Biedl Syndrome

KW - Cell Movement

KW - Ciliary Motility Disorders

KW - Craniofacial Abnormalities

KW - Disease Models, Animal

KW - Fibroblast Growth Factor 8

KW - Intracellular Signaling Peptides and Proteins

KW - Kruppel-Like Transcription Factors

KW - Maxilla

KW - Mice

KW - Mice, Mutant Strains

KW - Neural Crest

KW - Orofaciodigital Syndromes

KW - Palate

KW - Phenotype

U2 - 10.1016/j.devcel.2013.05.021

DO - 10.1016/j.devcel.2013.05.021

M3 - Article

C2 - 23806618

SN - 1534-5807

VL - 25

SP - 623

EP - 635

JO - Developmental Cell

JF - Developmental Cell

IS - 6

ER -

Fuz Mutant Mice Reveal Shared Mechanisms between Ciliopathies and FGF-Related Syndromes

Abstract

Keywords

UN SDGs

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