Journal article
Deletion of G protein-coupled receptor 48 leads to ocular anterior segment dysgenesis (ASD) through down-regulation of Pitx2
Proceedings of the National Academy of Sciences - PNAS, Vol.105(16), pp.6081-6086
04/18/2008
DOI: 10.1073/pnas.0708257105
PMCID: PMC2329706
PMID: 18424556
Abstract
The development of the anterior segment of the mammalian eye is critical for normal ocular function, whereas abnormal development can cause glaucoma, a leading cause of blindness in the world. We report that orphan G protein-coupled receptor 48 (Gpr48/LGR4) plays an important role in the development of the anterior segment structure. Disruption of
Gpr48
causes a wide spectrum of anterior segment dysgenesis (ASD), including microphthalmia, iris hypoplasia, irdiocorneal angle malformation, cornea dysgenesis, and cataract. Detailed analyses reveal that defective iris myogenesis and ocular extracellular matrix homeostasis are detected at early postnatal stages of eye development, whereas ganglion cell loss, inner nuclear layer thinness, and early onset of glaucoma were detected in 6-month-old
Gpr48
−/−
mice. To determine the molecular mechanism of ASD caused by the deletion of
Gpr48
, we performed gene expression analyses and revealed dramatic down-regulation of
Pitx2
in homozygous knockout mice.
In vitro
studies with the constitutively active Gpr48 mutant receptor demonstrate that Pitx2 is a direct target of the Gpr48-mediated cAMP-CREB signaling pathway in regulating anterior segment development, suggesting a role of Gpr48 as a potential therapeutic target of ASD.
Details
- Title: Subtitle
- Deletion of G protein-coupled receptor 48 leads to ocular anterior segment dysgenesis (ASD) through down-regulation of Pitx2
- Creators
- Jinsheng Weng - Texas A&M University SystemJian Luo - East China Normal UniversityXuhong Cheng - Texas A&M Health Science CenterChang Jin - Wenzhou Medical UniversityXiangtian Zhou - Wenzhou Medical UniversityJia Qu - Wenzhou Medical UniversityLiLi Tu - Wenzhou Medical UniversityDi Ai - Texas A&M Health Science CenterDali Li - East China Normal UniversityJun Wang - Texas A&M Health Science CenterJames F. Martin - Texas A&M Health Science CenterBrad A. Amendt - Texas A&M Health Science CenterMingyao Liu - East China Normal University
- Resource Type
- Journal article
- Publication Details
- Proceedings of the National Academy of Sciences - PNAS, Vol.105(16), pp.6081-6086
- DOI
- 10.1073/pnas.0708257105
- PMID
- 18424556
- PMCID
- PMC2329706
- NLM abbreviation
- Proc Natl Acad Sci U S A
- ISSN
- 0027-8424
- eISSN
- 1091-6490
- Publisher
- National Academy of Sciences
- Language
- English
- Date published
- 04/18/2008
- Academic Unit
- Orthodontics; Anatomy and Cell Biology; Craniofacial Anomalies Research Center; Dental Research
- Record Identifier
- 9984284330002771
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