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Malformation of Tear Ducts Underlies the Epiphora and Precocious Eyelid Opening in Prickle 1 Mutant Mice: Genetic Implications for Tear Duct Genesis

PURPOSE: Obstruction of the tear drainage causes a range of ocular surface disorders. Hitherto, the genetics of tear duct development and obstruction has been scarcely explored, and related animal models are lacking. This study aims to study the potential role of the Wnt/PCP pathway mediated by Pric...

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Autores principales: Ru, Jiali, Guo, Dianlei, Fan, Jiaying, Zhang, Jiao, Ju, Rong, Ouyang, Hong, Wei, Lai, Liu, Yizhi, Liu, Chunqiao
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Association for Research in Vision and Ophthalmology 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7645213/
https://www.ncbi.nlm.nih.gov/pubmed/33141892
http://dx.doi.org/10.1167/iovs.61.13.6
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author Ru, Jiali
Guo, Dianlei
Fan, Jiaying
Zhang, Jiao
Ju, Rong
Ouyang, Hong
Wei, Lai
Liu, Yizhi
Liu, Chunqiao
author_facet Ru, Jiali
Guo, Dianlei
Fan, Jiaying
Zhang, Jiao
Ju, Rong
Ouyang, Hong
Wei, Lai
Liu, Yizhi
Liu, Chunqiao
author_sort Ru, Jiali
collection PubMed
description PURPOSE: Obstruction of the tear drainage causes a range of ocular surface disorders. Hitherto, the genetics of tear duct development and obstruction has been scarcely explored, and related animal models are lacking. This study aims to study the potential role of the Wnt/PCP pathway mediated by Prickle 1 in tear duct development and diseases. METHODS: A severe hypomorphic Prickle 1 mutant was generated. Histology and immunohistochemistry were performed to compare wild type, Prickle 1 hypomorphic, and null mutant tear ducts. In situ hybridization was conducted to identify the signaling components in the developing tear ducts. Three-dimensional (3D) reconstruction was used to detect the human embryonic tear duct. RESULTS: Here, we report that a severe Prickle 1 hypomorph mouse line exhibited epiphora. This phenotype was due to the blockage of the tear drainage by incompletely formed nasolacrimal duct (NLD) and lacrimal canaliculi (LC), which also causes precocious eyelid opening. We observed a dose-dependent requirement of Prickle 1 for tear duct outgrowth. An investigation of the expression of Wnt/PCP core genes demonstrated a subset of PCP signaling components expressed in the developing tear duct. Furthermore, Prickle 1 is not required for the expression of Fgfr2/Fgf10 and p63 genes, which are associated with the NLD and LC hypoplasia in humans. Last, we showed that Prickle 1 expression in the developing tear drainage system is conserved between mice and humans. CONCLUSIONS: The study suggests that malformed tear ducts caused by disruption of Prickle 1 underlies the epiphora and precocious eyelid opening.
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spelling pubmed-76452132020-11-15 Malformation of Tear Ducts Underlies the Epiphora and Precocious Eyelid Opening in Prickle 1 Mutant Mice: Genetic Implications for Tear Duct Genesis Ru, Jiali Guo, Dianlei Fan, Jiaying Zhang, Jiao Ju, Rong Ouyang, Hong Wei, Lai Liu, Yizhi Liu, Chunqiao Invest Ophthalmol Vis Sci Anatomy and Pathology/Oncology PURPOSE: Obstruction of the tear drainage causes a range of ocular surface disorders. Hitherto, the genetics of tear duct development and obstruction has been scarcely explored, and related animal models are lacking. This study aims to study the potential role of the Wnt/PCP pathway mediated by Prickle 1 in tear duct development and diseases. METHODS: A severe hypomorphic Prickle 1 mutant was generated. Histology and immunohistochemistry were performed to compare wild type, Prickle 1 hypomorphic, and null mutant tear ducts. In situ hybridization was conducted to identify the signaling components in the developing tear ducts. Three-dimensional (3D) reconstruction was used to detect the human embryonic tear duct. RESULTS: Here, we report that a severe Prickle 1 hypomorph mouse line exhibited epiphora. This phenotype was due to the blockage of the tear drainage by incompletely formed nasolacrimal duct (NLD) and lacrimal canaliculi (LC), which also causes precocious eyelid opening. We observed a dose-dependent requirement of Prickle 1 for tear duct outgrowth. An investigation of the expression of Wnt/PCP core genes demonstrated a subset of PCP signaling components expressed in the developing tear duct. Furthermore, Prickle 1 is not required for the expression of Fgfr2/Fgf10 and p63 genes, which are associated with the NLD and LC hypoplasia in humans. Last, we showed that Prickle 1 expression in the developing tear drainage system is conserved between mice and humans. CONCLUSIONS: The study suggests that malformed tear ducts caused by disruption of Prickle 1 underlies the epiphora and precocious eyelid opening. The Association for Research in Vision and Ophthalmology 2020-11-03 /pmc/articles/PMC7645213/ /pubmed/33141892 http://dx.doi.org/10.1167/iovs.61.13.6 Text en Copyright 2020 The Authors http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License.
spellingShingle Anatomy and Pathology/Oncology
Ru, Jiali
Guo, Dianlei
Fan, Jiaying
Zhang, Jiao
Ju, Rong
Ouyang, Hong
Wei, Lai
Liu, Yizhi
Liu, Chunqiao
Malformation of Tear Ducts Underlies the Epiphora and Precocious Eyelid Opening in Prickle 1 Mutant Mice: Genetic Implications for Tear Duct Genesis
title Malformation of Tear Ducts Underlies the Epiphora and Precocious Eyelid Opening in Prickle 1 Mutant Mice: Genetic Implications for Tear Duct Genesis
title_full Malformation of Tear Ducts Underlies the Epiphora and Precocious Eyelid Opening in Prickle 1 Mutant Mice: Genetic Implications for Tear Duct Genesis
title_fullStr Malformation of Tear Ducts Underlies the Epiphora and Precocious Eyelid Opening in Prickle 1 Mutant Mice: Genetic Implications for Tear Duct Genesis
title_full_unstemmed Malformation of Tear Ducts Underlies the Epiphora and Precocious Eyelid Opening in Prickle 1 Mutant Mice: Genetic Implications for Tear Duct Genesis
title_short Malformation of Tear Ducts Underlies the Epiphora and Precocious Eyelid Opening in Prickle 1 Mutant Mice: Genetic Implications for Tear Duct Genesis
title_sort malformation of tear ducts underlies the epiphora and precocious eyelid opening in prickle 1 mutant mice: genetic implications for tear duct genesis
topic Anatomy and Pathology/Oncology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7645213/
https://www.ncbi.nlm.nih.gov/pubmed/33141892
http://dx.doi.org/10.1167/iovs.61.13.6
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