scholarly journals Epithelial flow into the optic cup facilitated by suppression of BMP drives eye morphogenesis

2014 ◽  
Author(s):  
Stephan Heermann ◽  
Lucas Schuetz ◽  
Steffen Lemke ◽  
Kerstin Krieglstein ◽  
Joachim Wittbrodt
Keyword(s):  
Morphological Changes ◽  
Fold Increase ◽  
Optic Vesicle ◽  
Retinal Pigmented Epithelium ◽  
Basal Surface ◽  
Classical View ◽  
Optic Cup ◽  
Pigmented Epithelium ◽  
Vertebrate Eye ◽  
Eye Morphogenesis

The transformation of the oval optic vesicle to a hemispheric bi-layered optic cup involves major morphological changes during early vertebrate eye development. According to the classical view, the lens-averted epithelium differentiates into the retinal pigmented epithelium (RPE), while the lens-facing epithelium forms the neuroretina. We find a 4.7 fold increase of the entire basal surface of the optic cup. Although the area an individual RPC demands at its basal surface declines during optic cup formation, we find a 4.7 fold increase of the entire basal surface of the optic cup. We demonstrate that the lens-averted epithelium functions as reservoir and contributes to the growing neuroretina by epithelial flow around the distal rims of the optic cup. This flow is negatively modulated by BMP, which arrests epithelial flow. This inhibition results in persisting neuroretina in the RPE domain and ultimately in coloboma.

scholarly journals Eye morphogenesis driven by epithelial flow into the optic cup facilitated by modulation of bone morphogenetic protein

eLife ◽  
2015 ◽  
Vol 4 ◽  
Author(s):  
Stephan Heermann ◽  
Lucas Schütz ◽  
Steffen Lemke ◽  
Kerstin Krieglstein ◽  
Joachim Wittbrodt
Keyword(s):  
Marginal Zone ◽  
Eye Development ◽  
Optic Vesicle ◽  
Basal Surface ◽  
Morphogenetic Protein ◽  
Retinal Determination ◽  
Optic Cup ◽  
Morphological Transformations ◽  
Vertebrate Eye ◽  
Ciliary Marginal Zone

The hemispheric, bi-layered optic cup forms from an oval optic vesicle during early vertebrate eye development through major morphological transformations. The overall basal surface, facing the developing lens, is increasing, while, at the same time, the space basally occupied by individual cells is decreasing. This cannot be explained by the classical view of eye development. Using zebrafish (Danio rerio) as a model, we show that the lens-averted epithelium functions as a reservoir that contributes to the growing neuroretina through epithelial flow around the distal rims of the optic cup. We propose that this flow couples morphogenesis and retinal determination. Our 4D data indicate that future stem cells flow from their origin in the lens-averted domain of the optic vesicle to their destination in the ciliary marginal zone. BMP-mediated inhibition of the flow results in ectopic neuroretina in the RPE domain. Ultimately the ventral fissure fails to close resulting in coloboma.

scholarly journals Build me up optic cup: Intrinsic and extrinsic mechanisms of vertebrate eye morphogenesis

2021 ◽  
Vol 476 ◽  
pp. 128-136
Author(s):  
Macaulie A. Casey ◽  
Sarah Lusk ◽  
Kristen M. Kwan
Keyword(s):  
Optic Cup ◽  
Vertebrate Eye ◽  
Eye Morphogenesis

The Msh-like homeobox genes define domains in the developing vertebrate eye

Development ◽  
1991 ◽  
Vol 112 (4) ◽  
pp. 1053-1061 ◽  
Author(s):  
A.P. Monaghan ◽  
D.R. Davidson ◽  
C. Sime ◽  
E. Graham ◽  
R. Baldock ◽  
...  
Keyword(s):  
Mouse Embryo ◽  
Ciliary Body ◽  
Cellular Differentiation ◽  
Temporal Relationship ◽  
Chromosomal Location ◽  
Neural Retina ◽  
Optic Vesicle ◽  
Surface Ectoderm ◽  
Optic Cup ◽  
Vertebrate Eye

The mouse Hox-7.1 gene has previously been shown to be related to the Drosophila Msh homeobox-containing gene. Here we report the isolation of a new member of this family which resides at an unlinked chromosomal location and has been designated Hox-8.1. Both Hox-7.1 and Hox-8.1 are expressed in the mouse embryo during the early stages of eye development in a distinct spatial and temporal relationship. Hox-8.1 is expressed in the surface ectoderm and in the optic vesicle before invagination occurs in regions corresponding to the prospective corneal epithelium and neural retina, respectively. Hox-7.1 is expressed after formation of the optic cup, marking the domain that will give rise to the ciliary body. The activity of these genes indicates that the inner layer of the optic cup is differentiated into three distinct compartments before overt cellular differentiation occurs. Our results suggest that these genes are involved in defining the region that gives rise to the inner layer of the optic cup and in patterning this tissue to define the iris, ciliary body and retina.

scholarly journals Developmental delay during eye morphogenesis underlies optic cup and neurogenesis defects in mab21l2u517 zebrafish mutants

2020 ◽  
Vol 52 ◽  
Author(s):  
Rebecca Wycliffe ◽  
Julie Plaisancie ◽  
Sydney Leaman ◽  
Octavia Santis ◽  
Lisa Tucker ◽  
...  
Keyword(s):  
Developmental Delay ◽  
Marginal Zone ◽  
Tissue Cell ◽  
Asynchronous Development ◽  
Optic Cup ◽  
Organ Specific ◽  
Optic Vesicles ◽  
Vertebrate Eye ◽  
Ciliary Marginal Zone ◽  
Eye Morphogenesis

Background: Shaping the vertebrate eye requires evagination of the optic vesicles. These vesicles subsequently fold into optic cups prior to undergoing neurogenesis and allocating a population of late progenitors at the margin of the eye. mab21l2 encodes a protein of unknown biological function expressed in the developing optic vesicles, and loss of mab21l2 function results in malformed eyes. The bases of these defects are, however, poorly understood. Methods: To further study mab21l2 we used CRISPR/Cas9 to generate a new zebrafish mutant allele (mab21l2u517). We characterized eye morphogenesis and neurogenesis upon loss of mab21l2 function using tissue/cell-type-specific transgenes and immunostaining, in situ hybridization and bromodeoxyuridine incorporation. Results: mab21l2u517 eyes fail to grow properly and display an excess of progenitors in the ciliary marginal zone. The expression of a transgene reporter for the vsx2 gene –a conserved marker for retinal progenitors– was delayed in mutant eyes and accompanied by disruptions in the epithelial folding that fuels optic cup morphogenesis. Mutants also displayed nasal-temporal malformations suggesting asynchronous development along that axis. Consistently, nasal retinal neurogenesis initiated but did not propagate in a timely fashion to the temporal retina. Later in development, mutant retinas did laminate and differentiate. Thus, mab21l2u517 mutants present a complex eye morphogenesis phenotype characterized by an organ-specific developmental delay. Conclusions: We propose that mab21l2 facilitates optic cup development with consequences both for timely neurogenesis and allocation of progenitors to the zebrafish ciliary marginal zone. These results confirm and extend previous analyses supporting the role of mab21l2 in coordinating morphogenesis and differentiation in developing eyes.

Extraocular mesenchyme patterns the optic vesicle during early eye development in the embryonic chick

Development ◽  
2000 ◽  
Vol 127 (21) ◽  
pp. 4599-4609 ◽  
Author(s):  
S. Fuhrmann ◽  
E.M. Levine ◽  
T.A. Reh
Keyword(s):  
Matrix Protein ◽  
Eye Development ◽  
Neural Retina ◽  
Optic Vesicle ◽  
Lateral Plate ◽  
Surface Ectoderm ◽  
Eye Growth ◽  
Pigmented Epithelium ◽  
Optic Vesicles ◽  
Vertebrate Eye

The vertebrate eye develops from the neuroepithelium of the ventral forebrain by the evagination and formation of the optic vesicle. Classical embryological studies have shown that the surrounding extraocular tissues - the surface ectoderm and extraocular mesenchyme - are necessary for normal eye growth and differentiation. We have used explant cultures of chick optic vesicles to study the regulation of retinal pigmented epithelium (RPE) patterning and differentiation during early eye development. Our results show that extraocular mesenchyme is required for the induction and maintenance of expression of the RPE-specific genes Mitf and Wnt13 and the melanosomal matrix protein MMP115. In the absence of extraocular tissues, RPE development did not occur. Replacement of the extraocular mesenchyme with cranial mesenchyme, but not lateral plate mesoderm, could rescue expression of the RPE-marker Mitf. In addition to activating expression of RPE-specific genes, the extraocular mesenchyme inhibits the expression of the neural retina-specific transcription factor Chx10 and downregulates the eye-specific transcription factors Pax6 and Optx2. The TGF(β) family member activin can substitute for the extraocular mesenchyme by promoting expression of the RPE-specific genes and downregulating expression of the neural retina-specific markers. These data indicate that extraocular mesenchyme, and possibly an activin-like signal, pattern the domains of the optic vesicle into RPE and neural retina.

scholarly journals Nf2 fine-tunes proliferation and tissue alignment during closure of the optic fissure in the embryonic mouse eye

2020 ◽  
Vol 29 (20) ◽  
pp. 3373-3387
Author(s):  
Wesley R Sun ◽  
Sara Ramirez ◽  
Kelly E Spiller ◽  
Yan Zhao ◽  
Sabine Fuhrmann
Keyword(s):  
Cell Fate ◽  
Hippo Pathway ◽  
Cell Number ◽  
Cancer Development ◽  
Developmentally Regulated ◽  
Embryonic Mouse ◽  
Ocular Abnormalities ◽  
Optic Cup ◽  
Pigmented Epithelium ◽  
Eye Morphogenesis

Abstract Uveal coloboma represents one of the most common congenital ocular malformations accounting for up to 10% of childhood blindness (~1 in 5000 live birth). Coloboma originates from defective fusion of the optic fissure (OF), a transient gap that forms during eye morphogenesis by asymmetric, ventral invagination. Genetic heterogeneity combined with the activity of developmentally regulated genes suggests multiple mechanisms regulating OF closure. The tumor suppressor and FERM domain protein Neurofibromin 2 (NF2) controls diverse processes in cancer, development and regeneration, via Hippo pathway and cytoskeleton regulation. In humans, NF2 mutations can cause ocular abnormalities, including coloboma, however, its actual role in OF closure is unknown. Using conditional inactivation in the embryonic mouse eye, our data indicate that loss of Nf2 function results in a novel underlying cause for coloboma. In particular, mutant eyes show substantially increased retinal pigmented epithelium (RPE) proliferation in the fissure region with concomitant acquisition of RPE cell fate. Cells lining the OF margin can maintain RPE fate ectopically and fail to transition from neuroepithelial to cuboidal shape. In the dorsal RPE of the optic cup, Nf2 inactivation leads to a robust increase in cell number, with local disorganization of the cytoskeleton components F-actin and pMLC2. We propose that RPE hyperproliferation is the primary cause for the observed defects causing insufficient alignment of the OF margins in Nf2 mutants and failure to fuse properly, resulting in persistent coloboma. Our findings indicate that limiting proliferation particularly in the RPE layer is a critical mechanism during OF closure.

scholarly journals EFFECTS OF CYCLIC AMP AND SEPHADEX FRACTIONS OF CHICK EMBRYO EXTRACT ON CLONED RETINAL PIGMENTED EPITHELIUM IN TISSUE CULTURE

1974 ◽  
Vol 61 (2) ◽  
pp. 369-382 ◽  
Author(s):  
D. A. Newsome ◽  
R. T. Fletcher ◽  
W. G. Robison ◽  
K. R. Kenyon ◽  
G. J. Chader
Keyword(s):  
Molecular Weight ◽  
Chick Embryo ◽  
Adenosine Monophosphate ◽  
Cell Number ◽  
Retinal Pigmented Epithelium ◽  
Culture Dish ◽  
Adhesive Properties ◽  
Embryo Extract ◽  
Chick Embryo Extract ◽  
Pigmented Epithelium

The effects of dibutyryl cyclic 3',5'-adenosine monophosphate (BcAMP) and Sephadex G-25 fractions of chick embryo extract on the growth rate, morphology, and pigmentation of normal chick retinal pigmented epithelium (PE) were investigated. Seven cloned PE cell lines were each grown in modified Ham's F-12 medium alone (F-12), or in F-12 supplemented with either high molecular weight (H) or low molecular weight (L) fractions of chick embryo extract. Cells grown in F-12 alone or in L medium formed compact epithelial sheets, whereas cells grown in H had a fibrocytic appearance and formed poorly organized monolayers. In H plus BcAMP, cell morphology was more epithelioid than in H alone, and generally the monolayers appeared more differentiated. Under each of these three culture conditions, 2 x 10-4 M BCAMP retarded the increase in cell number and decreased the final number of cells per culture dish, but had little effect on plating efficiency. BcAMP also increased the rate of cell adhesion to a plastic substratum. Pigmentation was marked in cultures grown in F-12 or in L alone, but the addition of BcAMP dramatically reduced visible pigmentation. This effect was reversed when BcAMP was removed from the culture medium. Thus BcAMP modifies cell and colonial morphology, rate of cell accumulation, adhesive properties, and pigmentation of normal PE cells.

The Xenopus homologue of the Drosophila gene tailless has a function in early eye development

Development ◽  
1998 ◽  
Vol 125 (13) ◽  
pp. 2425-2432 ◽  
Author(s):  
T. Hollemann ◽  
E. Bellefroid ◽  
T. Pieler
Keyword(s):  
Eye Development ◽  
Neural Plate ◽  
Regulatory Function ◽  
Genetic Circuits ◽  
Optic Stalk ◽  
Drosophila Gene ◽  
Ciliary Margin ◽  
Evolutionarily Conserved ◽  
Optic Cup ◽  
Vertebrate Eye

Genetic circuits responsible for the development of photoreceptive organs appear to be evolutionarily conserved. Here, the Xenopus homologue Xtll of the Drosophila gene tailless (tll), which we find to be expressed during early eye development, is characterized with respect to its relationship to vertebrate regulators of eye morphogenesis, such as Pax6 and Rx. Expression of all three genes is first detected in the area corresponding to the eye anlagen within the open neural plate in partially overlapping, but not identical, patterns. During the evagination of the optic vesicle, Xtll expression is most prominent in the optic stalk, as well as in the distal tip of the forming vesicle. In tadpole-stage embryos, Xtll gene transcription is most prominent in the ciliary margin of the optic cup. Inhibition of Xtll function in Xenopus embryos interferes specifically with the evagination of the eye vesicle and, in consequence, Xpax6 gene expression is severely reduced in such manipulated embryos. These findings suggest that Xtll serves an important regulatory function in the earliest phases of vertebrate eye development.

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