The Experts below are selected from a list of 297 Experts worldwide ranked by ideXlab platform
Zbynek Kozmik - One of the best experts on this subject based on the ideXlab platform.
-
Stage-dependent requirement of neuroretinal Pax6 for lens and retina development
Development, 2014Co-Authors: Lucie Klimova, Zbynek KozmikAbstract:The physical contact of optic vesicle with head Surface Ectoderm is an initial event triggering eye morphogenesis. This interaction leads to lens specification followed by coordinated invagination of the lens placode and optic vesicle, resulting in formation of the lens, retina and retinal pigmented epithelium. Although the role of Pax6 in early lens development has been well documented, its role in optic vesicle neuroepithelium and early retinal progenitors is poorly understood. Here we show that conditional inactivation of Pax6 at distinct time points of mouse neuroretina development has a different impact on early eye morphogenesis. When Pax6 is eliminated in the retina at E10.5 using an mRx-Cre transgene, after a sufficient contact between the optic vesicle and Surface Ectoderm has occurred, the lens develops normally but the pool of retinal progenitor cells gradually fails to expand. Furthermore, a normal differentiation program is not initiated, leading to almost complete disappearance of the retina after birth. By contrast, when Pax6 was inactivated at the onset of contact between the optic vesicle and Surface Ectoderm in Pax6Sey/flox embryos, expression of lens-specific genes was not initiated and neither the lens nor the retina formed. Our data show that Pax6 in the optic vesicle is important not only for proper retina development, but also for lens formation in a non-cell-autonomous manner.
-
lens morphogenesis is dependent on pax6 mediated inhibition of the canonical wnt beta catenin signaling in the lens Surface Ectoderm
Genesis, 2009Co-Authors: Ondrej Machon, Jana Kreslova, Jana Ruzickova, Tomas Vacik, Lucie Klimova, Naoko Fujimura, Jitka Lachova, Zbynek KozmikAbstract:Lens formation in mouse is critically dependent on proper development of the retinal neuroEctoderm that is located close beneath the head Surface Ectoderm. Signaling from the prospective retina triggers lens-specific gene expression in the Surface-Ectoderm. Supression of canonical Wnt/β-catenin signaling in the Surface Ectoderm is one of the prerequisites for lens development because, as we show here, ectopic Wnt activation in the retina and lens abrogates lens formation. Wnt inhibiton is mediated by signals coming from the retina but its exact mechanism is unknown. We show that Pax6 directly controls expression of several Wnt inhibitors such as Sfrp1, Sfrp2, and Dkk1 in the presumptive lens. In accordance, absence of Pax6 function leads to aberrant canonical Wnt activity in the presumptive lens that subsequently impairs lens development. Thus Pax6 is required for down-regulation of canonical Wnt signaling in the presumptive lens Ectoderm. genesis 48:86–95, 2010. © 2009 Wiley-Liss, Inc.
-
Lens morphogenesis is dependent on Pax6-mediated inhibition of the canonical Wnt/beta-catenin signaling in the lens Surface Ectoderm.
Genesis, 2009Co-Authors: Ondrej Machon, Jana Kreslova, Jana Ruzickova, Tomas Vacik, Lucie Klimova, Naoko Fujimura, Jitka Lachova, Zbynek KozmikAbstract:Lens formation in mouse is critically dependent on proper development of the retinal neuroEctoderm that is located close beneath the head Surface Ectoderm. Signaling from the prospective retina triggers lens-specific gene expression in the Surface-Ectoderm. Supression of canonical Wnt/β-catenin signaling in the Surface Ectoderm is one of the prerequisites for lens development because, as we show here, ectopic Wnt activation in the retina and lens abrogates lens formation. Wnt inhibiton is mediated by signals coming from the retina but its exact mechanism is unknown. We show that Pax6 directly controls expression of several Wnt inhibitors such as Sfrp1, Sfrp2, and Dkk1 in the presumptive lens. In accordance, absence of Pax6 function leads to aberrant canonical Wnt activity in the presumptive lens that subsequently impairs lens development. Thus Pax6 is required for down-regulation of canonical Wnt signaling in the presumptive lens Ectoderm. genesis 48:86–95, 2010. © 2009 Wiley-Liss, Inc.
J Zhang - One of the best experts on this subject based on the ideXlab platform.
-
role of smad4 from ocular Surface Ectoderm in retinal vasculature development
International Journal of Ophthalmology, 2020Co-Authors: Jing Li, J Zhang, Jiangyue ZhaoAbstract:AIM: To investigate how signals from lens regulate retinal vascular development and neovascularization. METHODS: Le-Cre transgenic mouse line was employed to inactivate Smad4 in the Surface Ectoderm selectively. Standard histological and whole-mount retina staining were employed to reveal morphological changes of retinal vasculature in Smad4 defective eye. cDNA microarray and subsequent analyses were conducted to investigate the molecular mechanism underlying the vascular phenotype. Quantitative polymerase chain reaction (qPCR) was carried out to verify the microarrays results. RESULTS: We found that inactivation of Smad4 specifically on Surface Ectoderm leads to a variety of retinal vasculature anomalies. Microarray analyses and qPCR revealed that Sema3c, Sema3e, Nrp1, Tie1, Sox7, Sox17, and Sox18 are significantly affected in the knockout retinas at different developmental stages, suggesting that ocular Surface Ectoderm-derived Smad4 can signal to the retina and regulates various angiogenic signaling in the retina. CONCLUSION: Our data suggest that the cross-talk between ocular Surface Ectoderm and retina is important for retinal vasculature development, and Smad4 regulates various signaling associated with sprouting angiogenesis, vascular remodeling and maturation in the retina of mice.
-
embryonic Surface Ectoderm specific mitofusin 2 conditional knockout induces congenital cataracts in mice
Scientific Reports, 2018Co-Authors: Jiangyue Zhao, Xinwei Wu, Danhong Wu, Yinhui Yu, Yibo Yu, Yao Wang, Qiuli Fu, J ZhangAbstract:Inherited mitochondrial mutations can result in mitochondrial dysfunction or stochastic oxidative damage. Cumulative mitochondrial damage is an important factor in age-related disorders, such as cataracts and macular degeneration. Mfn2 mediates the fusion of mitochondria and contribute to the dynamic balance between fusion and fission that determines mitochondria morphology. We report here that conditional loss of Mfn2 function in the head Surface Ectoderm leads to a range of congenital eye defects, including small, opacified lens and small eyeball in the most severe phenotypes. The Le-Cre transgenic mouse line and Mfn2 flox mouse line were used in this study to generate Mfn2 conditional knockout mice. Our study revealed Mfn2 gene function in lens development and addressed the relationship between the mitochondria and lens transparency. Conditional loss of Mfn2 affected lens epithelium cell proliferation, apoptosis and ultrastructure of mitochondria. We conclude that proper development of the lens and lens transparency depend on normal Mfn2 gene function.
-
requirement of smad4 from ocular Surface Ectoderm for retinal development
PLOS ONE, 2016Co-Authors: Jing Li, Jiangyue Zhao, Shusheng Wang, Chastain Anderson, Fangkun Zhao, Di Wu, Xinwei Wu, Xuefei He, J ZhangAbstract:Microphthalmia is characterized by abnormally small eyes and usually retinal dysplasia, accounting for up to 11% of the blindness in children. Right now there is no effective treatment for the disease, and the underlying mechanisms, especially how retinal dysplasia develops from microphthalmia and whether it depends on the signals from lens Ectoderm are still unclear. Mutations in genes of the TGF-β superfamily have been noted in patients with microphthalmia. Using conditional knockout mice, here we address the question that whether ocular Surface Ectoderm-derived Smad4 modulates retinal development. We found that loss of Smad4 specifically on Surface lens Ectoderm leads to microphthalmia and dysplasia of retina. Retinal dysplasia in the knockout mice is caused by the delayed or failed differentiation and apoptosis of retinal cells. Microarray analyses revealed that members of Hedgehog and Wnt signaling pathways are affected in the knockout retinas, suggesting that ocular Surface Ectoderm-derived Smad4 can regulate Hedgehog and Wnt signaling in the retina. Our studies suggest that defective of ocular Surface Ectoderm may affect retinal development.
Richard A Lang - One of the best experts on this subject based on the ideXlab platform.
-
wnt ligands from the embryonic Surface Ectoderm regulate bimetallic strip optic cup morphogenesis in mouse
Development, 2015Co-Authors: April C Carpenter, April N Smith, Heidi Wagner, Yamit Cohentayar, Valerie A Wallace, Ruth Asherypadan, Richard A LangAbstract:The Wnt/β-catenin response pathway is central to many developmental processes. Here, we assessed the role of Wnt signaling in early eye development using the mouse as a model system. We showed that the Surface Ectoderm region that includes the lens placode expressed 12 out of 19 possible Wnt ligands. When these activities were suppressed by conditional deletion of wntless (Le-cre; Wlsfl/fl) there were dramatic consequences that included a saucer-shaped optic cup, ventral coloboma, and a deficiency of periocular mesenchyme. This phenotype shared features with that produced when the Wnt/β-catenin pathway co-receptor Lrp6 is mutated or when retinoic acid (RA) signaling in the eye is compromised. Consistent with this, microarray and cell fate marker analysis identified a series of expression changes in genes known to be regulated by RA or by the Wnt/β-catenin pathway. Using pathway reporters, we showed that Wnt ligands from the Surface Ectoderm directly or indirectly elicit a Wnt/β-catenin response in retinal pigment epithelium (RPE) progenitors near the optic cup rim. In Le-cre; Wlsfl/fl mice, the numbers of RPE cells are reduced and this can explain, using the principle of the bimetallic strip, the curvature of the optic cup. These data thus establish a novel hypothesis to explain how differential cell numbers in a bilayered epithelium can lead to shape change.
-
Distinct Requirements for Cranial Ectoderm and Mesenchyme-Derived Wnts in Specification and Differentiation of Osteoblast and Dermal Progenitors
PLOS Genetics, 2014Co-Authors: L. Henry Goodnough, Richard A Lang, Gregg J. Dinuoscio, James Ferguson, Trevor Williams, Radhika P. AtitAbstract:The cranial bones and dermis differentiate from mesenchyme beneath the Surface Ectoderm. Fate selection in cranial mesenchyme requires the canonical Wnt effector molecule β-catenin, but the relative contribution of Wnt ligand sources in this process remains unknown. Here we show Wnt ligands are expressed in cranial Surface Ectoderm and underlying supraorbital mesenchyme during dermal and osteoblast fate selection. Using conditional genetics, we eliminate secretion of all Wnt ligands from cranial Surface Ectoderm or undifferentiated mesenchyme, to uncover distinct roles for Ectoderm- and mesenchyme-derived Wnts. Ectoderm Wnt ligands induce osteoblast and dermal fibroblast progenitor specification while initiating expression of a subset of mesenchymal Wnts. Mesenchyme Wnt ligands are subsequently essential during differentiation of dermal and osteoblast progenitors. Finally, Ectoderm-derived Wnt ligands provide an inductive cue to the cranial mesenchyme for the fate selection of dermal fibroblast and osteoblast lineages. Thus two sources of Wnt ligands perform distinct functions during osteoblast and dermal fibroblast formation.
Jiangyue Zhao - One of the best experts on this subject based on the ideXlab platform.
-
role of smad4 from ocular Surface Ectoderm in retinal vasculature development
International Journal of Ophthalmology, 2020Co-Authors: Jing Li, J Zhang, Jiangyue ZhaoAbstract:AIM: To investigate how signals from lens regulate retinal vascular development and neovascularization. METHODS: Le-Cre transgenic mouse line was employed to inactivate Smad4 in the Surface Ectoderm selectively. Standard histological and whole-mount retina staining were employed to reveal morphological changes of retinal vasculature in Smad4 defective eye. cDNA microarray and subsequent analyses were conducted to investigate the molecular mechanism underlying the vascular phenotype. Quantitative polymerase chain reaction (qPCR) was carried out to verify the microarrays results. RESULTS: We found that inactivation of Smad4 specifically on Surface Ectoderm leads to a variety of retinal vasculature anomalies. Microarray analyses and qPCR revealed that Sema3c, Sema3e, Nrp1, Tie1, Sox7, Sox17, and Sox18 are significantly affected in the knockout retinas at different developmental stages, suggesting that ocular Surface Ectoderm-derived Smad4 can signal to the retina and regulates various angiogenic signaling in the retina. CONCLUSION: Our data suggest that the cross-talk between ocular Surface Ectoderm and retina is important for retinal vasculature development, and Smad4 regulates various signaling associated with sprouting angiogenesis, vascular remodeling and maturation in the retina of mice.
-
embryonic Surface Ectoderm specific mitofusin 2 conditional knockout induces congenital cataracts in mice
Scientific Reports, 2018Co-Authors: Jiangyue Zhao, Xinwei Wu, Danhong Wu, Yinhui Yu, Yibo Yu, Yao Wang, Qiuli Fu, J ZhangAbstract:Inherited mitochondrial mutations can result in mitochondrial dysfunction or stochastic oxidative damage. Cumulative mitochondrial damage is an important factor in age-related disorders, such as cataracts and macular degeneration. Mfn2 mediates the fusion of mitochondria and contribute to the dynamic balance between fusion and fission that determines mitochondria morphology. We report here that conditional loss of Mfn2 function in the head Surface Ectoderm leads to a range of congenital eye defects, including small, opacified lens and small eyeball in the most severe phenotypes. The Le-Cre transgenic mouse line and Mfn2 flox mouse line were used in this study to generate Mfn2 conditional knockout mice. Our study revealed Mfn2 gene function in lens development and addressed the relationship between the mitochondria and lens transparency. Conditional loss of Mfn2 affected lens epithelium cell proliferation, apoptosis and ultrastructure of mitochondria. We conclude that proper development of the lens and lens transparency depend on normal Mfn2 gene function.
-
requirement of smad4 from ocular Surface Ectoderm for retinal development
PLOS ONE, 2016Co-Authors: Jing Li, Jiangyue Zhao, Shusheng Wang, Chastain Anderson, Fangkun Zhao, Di Wu, Xinwei Wu, Xuefei He, J ZhangAbstract:Microphthalmia is characterized by abnormally small eyes and usually retinal dysplasia, accounting for up to 11% of the blindness in children. Right now there is no effective treatment for the disease, and the underlying mechanisms, especially how retinal dysplasia develops from microphthalmia and whether it depends on the signals from lens Ectoderm are still unclear. Mutations in genes of the TGF-β superfamily have been noted in patients with microphthalmia. Using conditional knockout mice, here we address the question that whether ocular Surface Ectoderm-derived Smad4 modulates retinal development. We found that loss of Smad4 specifically on Surface lens Ectoderm leads to microphthalmia and dysplasia of retina. Retinal dysplasia in the knockout mice is caused by the delayed or failed differentiation and apoptosis of retinal cells. Microarray analyses revealed that members of Hedgehog and Wnt signaling pathways are affected in the knockout retinas, suggesting that ocular Surface Ectoderm-derived Smad4 can regulate Hedgehog and Wnt signaling in the retina. Our studies suggest that defective of ocular Surface Ectoderm may affect retinal development.
Kohji Nishida - One of the best experts on this subject based on the ideXlab platform.
-
Coordinated generation of multiple ocular-like cell lineages and fabrication of functional corneal epithelial cell sheets from human iPS cells
Nature Protocols, 2017Co-Authors: Ryuhei Hayashi, Yuki Ishikawa, Ryousuke Katori, Yuzuru Sasamoto, Yuki Taniwaki, Hiroshi Takayanagi, Motokazu Tsujikawa, Kiyotoshi Sekiguchi, Andrew J Quantock, Kohji NishidaAbstract:We describe a protocol for the generation of a functional and transplantable corneal epithelium derived from human induced pluripotent stem (iPS) cells. When this protocol is followed, a proportion of iPS cells spontaneously form circular colonies, each of which is composed of four concentric zones. Cells in these zones have different morphologies and immunostaining characteristics, resembling neuroEctoderm, neural crest, ocular-Surface Ectoderm, or Surface Ectoderm. We have named this 2D colony a 'SEAM' (self-formed Ectodermal autonomous multizone), and previously demonstrated that cells within the SEAM have the potential to give rise to anlages of different ocular lineages, including retinal cells, lens cells, and ocular-Surface Ectoderm. To investigate the translational potential of the SEAM, cells within it that resemble ocular-Surface epithelia can be isolated by pipetting and FACS sorting into a population of corneal epithelial-like progenitor cells. These can be expanded and differentiated to form an epithelial layer expressing K12 and PAX6, and able to recover function in an animal model of corneal epithelial dysfunction after surgical transplantation. The whole protocol, encompassing human iPS cell preparation, autonomous differentiation, purification, and subsequent differentiation, takes between 100 and 120 d, and is of potential use to researchers with an interest in eye development and/or ocular-Surface regeneration. Experience with human iPS cell culture and sorting via FACS will be of benefit for researchers performing this protocol. This protocol describes how to grow a functional and transplantable corneal epithelium and how to generate ocular-like cell lineages resembling neuroEctoderm, neural crest, ocular-Surface Ectoderm, or Surface Ectoderm derived from human iPS cells.
-
Coordinated generation of multiple ocular-like cell lineages and fabrication of functional corneal epithelial cell sheets from human iPS cells
Nature Protocols, 2017Co-Authors: Ryuhei Hayashi, Yuki Ishikawa, Ryousuke Katori, Yuzuru Sasamoto, Yuki Taniwaki, Hiroshi Takayanagi, Motokazu Tsujikawa, Kiyotoshi Sekiguchi, Andrew J Quantock, Kohji NishidaAbstract:We describe a protocol for the generation of a functional and transplantable corneal epithelium derived from human induced pluripotent stem (iPS) cells. When this protocol is followed, a proportion of iPS cells spontaneously form circular colonies, each of which is composed of four concentric zones. Cells in these zones have different morphologies and immunostaining characteristics, resembling neuroEctoderm, neural crest, ocular-Surface Ectoderm, or Surface Ectoderm. We have named this 2D colony a 'SEAM' (self-formed Ectodermal autonomous multizone), and previously demonstrated that cells within the SEAM have the potential to give rise to anlages of different ocular lineages, including retinal cells, lens cells, and ocular-Surface Ectoderm. To investigate the translational potential of the SEAM, cells within it that resemble ocular-Surface epithelia can be isolated by pipetting and FACS sorting into a population of corneal epithelial-like progenitor cells. These can be expanded and differentiated to form an epithelial layer expressing K12 and PAX6, and able to recover function in an animal model of corneal epithelial dysfunction after surgical transplantation. The whole protocol, encompassing human iPS cell preparation, autonomous differentiation, purification, and subsequent differentiation, takes between 100 and 120 d, and is of potential use to researchers with an interest in eye development and/or ocular-Surface regeneration. Experience with human iPS cell culture and sorting via FACS will be of benefit for researchers performing this protocol.
