Journal article
Fuz Regulates Craniofacial Development through Tissue Specific Responses to Signaling Factors
PloS one, Vol.6(9), e24608
09/14/2011
DOI: 10.1371/journal.pone.0024608
PMCID: PMC3173472
PMID: 21935430
Abstract
The planar cell polarity effector gene Fuz regulates ciliogenesis and Fuz loss of function studies reveal an array of embryonic phenotypes. However, cilia defects can affect many signaling pathways and, in humans, cilia defects underlie several craniofacial anomalies. To address this, we analyzed the craniofacial phenotype and signaling responses of the Fuz(-/-) mice. We demonstrate a unique role for Fuz in regulating both Hedgehog (Hh) and Wnt/beta-catenin signaling during craniofacial development. Fuz expression first appears in the dorsal tissues and later in ventral tissues and craniofacial regions during embryonic development coincident with cilia development. The Fuz(-/-) mice exhibit severe craniofacial deformities including anophthalmia, agenesis of the tongue and incisors, a hypoplastic mandible, cleft palate, ossification/skeletal defects and hyperplastic malformed Meckel's cartilage. Hh signaling is down-regulated in the Fuz null mice, while canonical Wnt signaling is up-regulated revealing the antagonistic relationship of these two pathways. Meckel's cartilage is expanded in the Fuz(-/-) mice due to increased cell proliferation associated with the up-regulation of Wnt canonical target genes and decreased non-canonical pathway genes. Interestingly, cilia development was decreased in the mandible mesenchyme of Fuz null mice, suggesting that cilia may antagonize Wnt signaling in this tissue. Furthermore, expression of Fuz decreased expression of Wnt pathway genes as well as a Wnt-dependent reporter. Finally, chromatin IP experiments demonstrate that beta-catenin/TCF-binding directly regulates Fuz expression. These data demonstrate a new model for coordination of Hh and Wnt signaling and reveal a Fuz-dependent negative feedback loop controlling Wnt/beta-catenin signaling.
Details
- Title: Subtitle
- Fuz Regulates Craniofacial Development through Tissue Specific Responses to Signaling Factors
- Creators
- Zichao Zhang - Texas A&M Health Science CenterBogdan J. Wlodarczyk - The University of Texas at AustinKaren Niederreither - The University of Texas at AustinShankar Venugopalan - Texas A&M Health Science CenterSergio Florez - Texas A&M Health Science CenterRichard H. Finnell - The University of Texas at AustinBrad A. Amendt - Texas A&M Health Science Center
- Resource Type
- Journal article
- Publication Details
- PloS one, Vol.6(9), e24608
- DOI
- 10.1371/journal.pone.0024608
- PMID
- 21935430
- PMCID
- PMC3173472
- NLM abbreviation
- PLoS One
- ISSN
- 1932-6203
- eISSN
- 1932-6203
- Publisher
- Public Library Science
- Number of pages
- 16
- Grant note
- R01DE013941 / NATIONAL INSTITUTE OF DENTAL & CRANIOFACIAL RESEARCH; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Dental & Craniofacial Research (NIDCR) R01DE016315 / NATIONAL INSTITUTE OF DENTAL &CRANIOFACIAL RESEARCH; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Dental & Craniofacial Research (NIDCR) DE016315; DE13941; DE18885 / National Institutes of Health; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA
- Language
- English
- Date published
- 09/14/2011
- Academic Unit
- Orthodontics; Anatomy and Cell Biology; Craniofacial Anomalies Research Center; Dental Research
- Record Identifier
- 9984284350102771
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