scholarly journals Neural crest cells regulate optic cup morphogenesis by promoting extracellular matrix assembly

2018 ◽  
Author(s):  
Chase D. Bryan ◽  
Rebecca L. Pfeiffer ◽  
Bryan W. Jones ◽  
Kristen M. Kwan
Keyword(s):  
Extracellular Matrix ◽  
Neural Crest ◽  
Cell Tracking ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Neural Crest Cells ◽  
Underlying Mechanism ◽  
Ultrastructural Level ◽  
Matrix Assembly ◽  
Optic Cup

AbstractThe interactions between an organ and its surrounding environment are critical in regulating its development. In vertebrates, neural crest and mesodermal mesenchymal cells have been observed close to the eye during development, and mutations affecting this periocular mesenchyme can cause defects in early eye development, yet the underlying mechanism has been unknown. Here, using timelapse microscopy and four-dimensional cell tracking in zebrafish, we establish that genetic loss of neural crest impairs cell movements within the optic vesicle. At the ultrastructural level, neural crest cells are required for basement membrane formation specifically around the retinal pigment epithelium. Neural crest cells express the extracellular matrix crosslinking protein nidogen and, strikingly, ectopically expressing nidogen in the absence of neural crest partially restores optic cup morphogenesis. These results demonstrate that the neural crest is required for local establishment of ocular extracellular matrix superstructure, which in turn drives optic cup morphogenesis.

scholarly journals Primary cilia deficiency in neural crest cells models anterior segment dysgenesis in mouse

eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Céline Portal ◽  
Panteleimos Rompolas ◽  
Peter Lwigale ◽  
Carlo Iomini
Keyword(s):  
Neural Crest ◽  
Primary Cilia ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Anterior Segment ◽  
Neural Crest Cells ◽  
Corneal Neovascularization ◽  
Anterior Segment Dysgenesis ◽  
Chamber Volume ◽  
Signaling Axis

Defects affecting tissues of the anterior segment (AS) of the eye lead to a group of highly debilitating disorders called Anterior Segment Dysgenesis (ASD). Despite the identification of some causative genes, the pathogenesis of ASD remains unclear. Interestingly, several ciliopathies display conditions of the AS. Using conditional targeting of Ift88 with Wnt1-Cre, we show that primary cilia of neural crest cells (NCC), precursors of most AS structures, are indispensable for normal AS development and their ablation leads to ASD conditions including abnormal corneal dimensions, defective iridocorneal angle, reduced anterior chamber volume and corneal neovascularization. Mechanistically, NCC cilia ablation abolishes hedgehog (Hh) signaling in the periocular mesenchyme (POM) canonically activated by choroid-secreted Indian Hh, reduces proliferation of POM cells surrounding the retinal pigment epithelium and decreases the expression of Foxc1 and Pitx2, two transcription factors identified as major ASD causative genes. Thus, we uncovered a signaling axis linking cilia and ASD.

scholarly journals Pathogenic Effects of Mineralocorticoid Pathway Activation in Retinal Pigment Epithelium

2021 ◽  
Vol 22 (17) ◽  
pp. 9618
Author(s):  
Jérémie Canonica ◽  
Min Zhao ◽  
Tatiana Favez ◽  
Emmanuelle Gelizé ◽  
Laurent Jonet ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Retinal Pigment Epithelium ◽  
Barrier Function ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Retinal Diseases ◽  
Mesenchymal Transition ◽  
Rpe Cells ◽  
Pathway Activation ◽  
And Migration

Glucocorticoids are amongst the most used drugs to treat retinal diseases of various origins. Yet, the transcriptional regulations induced by glucocorticoid receptor (GR) and mineralocorticoid receptor (MR) activation in retinal pigment epithelium cells (RPE) that form the outer blood–retina barrier are unknown. Levels of endogenous corticoids, ligands for MR and GR, were measured in human ocular media. Human RPE cells derived from induced pluripotent stem cells (iRPE) were used to analyze the pan-transcriptional regulations induced by aldosterone—an MR-specific agonist, or cortisol or cortisol + RU486—a GR antagonist. The retinal phenotype of transgenic mice that overexpress the human MR (P1.hMR) was analyzed. In the human eye, the main ligand for GR and MR is cortisol. The iRPE cells express functional GR and MR. The subset of genes regulated by aldosterone and by cortisol + RU-486, and not by cortisol alone, mimics an imbalance toward MR activation. They are involved in extracellular matrix remodeling (CNN1, MGP, AMTN), epithelial–mesenchymal transition, RPE cell proliferation and migration (ITGB3, PLAUR and FOSL1) and immune balance (TNFSF18 and PTX3). The P1.hMR mice showed choroidal vasodilation, focal alteration of the RPE/choroid interface and migration of RPE cells together with RPE barrier function alteration, similar to human retinal diseases within the pachychoroid spectrum. RPE is a corticosteroid-sensitive epithelium. MR pathway activation in the RPE regulates genes involved in barrier function, extracellular matrix, neural regulation and epithelial differentiation, which could contribute to retinal pathology.

The role of bone morphogenetic proteins in the differentiation of the ventral optic cup

Development ◽  
2002 ◽  
Vol 129 (13) ◽  
pp. 3161-3171 ◽  
Author(s):  
Ruben Adler ◽  
Teri L. Belecky-Adams
Keyword(s):  
Bone Morphogenetic Proteins ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Ectopic Expression ◽  
Neural Retina ◽  
Optic Disk ◽  
Loss Of Function ◽  
In Ovo ◽  
Optic Stalk ◽  
Optic Cup

The ventral region of the chick embryo optic cup undergoes a complex process of differentiation leading to the formation of four different structures: the neural retina, the retinal pigment epithelium (RPE), the optic disk/optic stalk, and the pecten oculi. Signaling molecules such as retinoic acid and sonic hedgehog have been implicated in the regulation of these phenomena. We have now investigated whether the bone morphogenetic proteins (BMPs) also regulate ventral optic cup development. Loss-of-function experiments were carried out in chick embryos in ovo, by intraocular overexpression of noggin, a protein that binds several BMPs and prevents their interactions with their cognate cell surface receptors. At optic vesicle stages of development, this treatment resulted in microphthalmia with concomitant disruption of the developing neural retina, RPE and lens. At optic cup stages, however, noggin overexpression caused colobomas, pecten agenesis, replacement of the ventral RPE by neuroepithelium-like tissue, and ectopic expression of optic stalk markers in the region of the ventral retina and RPE. This was frequently accompanied by abnormal growth of ganglion cell axons, which failed to enter the optic nerve. The data suggest that endogenous BMPs have significant effects on the development of ventral optic cup structures.

nacre encodes a zebrafish microphthalmia-related protein that regulates neural-crest-derived pigment cell fate

Development ◽  
1999 ◽  
Vol 126 (17) ◽  
pp. 3757-3767 ◽  
Author(s):  
J.A. Lister ◽  
C.P. Robertson ◽  
T. Lepage ◽  
S.L. Johnson ◽  
D.W. Raible
Keyword(s):  
Transcription Factor ◽  
Retinal Pigment Epithelium ◽  
Neural Crest ◽  
Cell Fate ◽  
Pigment Cell ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Pigment Cells ◽  
Evolutionary Divergence ◽  
Wild Type

We report the isolation and identification of a new mutation affecting pigment cell fate in the zebrafish neural crest. Homozygous nacre (nac(w2)) mutants lack melanophores throughout development but have increased numbers of iridophores. The non-crest-derived retinal pigment epithelium is normal, suggesting that the mutation does not affect pigment synthesis per se. Expression of early melanoblast markers is absent in nacre mutants and transplant experiments suggested a cell-autonomous function in melanophores. We show that nac(w2) is a mutation in a zebrafish gene encoding a basic helix-loop-helix/leucine zipper transcription factor related to microphthalmia (Mitf), a gene known to be required for development of eye and crest pigment cells in the mouse. Transient expression of the wild-type nacre gene restored melanophore development in nacre(−/−) embryos. Furthermore, misexpression of nacre induced the formation of ectopic melanized cells and caused defects in eye development in wild-type and mutant embryos. These results demonstrate that melanophore development in fish and mammals shares a dependence on the nacre/Mitf transcription factor, but that proper development of the retinal pigment epithelium in the fish is not nacre-dependent, suggesting an evolutionary divergence in the function of this gene.

Patterning the Vertebrate Retina with Morphogenetic Signaling Pathways

2019 ◽  
Vol 26 (2) ◽  
pp. 185-196 ◽  
Author(s):  
Marcos J. Cardozo ◽  
María Almuedo-Castillo ◽  
Paola Bovolenta
Keyword(s):  
Signaling Pathways ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Subsequent Development ◽  
Neural Retina ◽  
Bmp Signaling ◽  
Vertebrate Species ◽  
Optic Stalk ◽  
Optic Cup ◽  
Vertebrate Eye

The primordium of the vertebrate eye is composed of a pseudostratified and apparently homogeneous neuroepithelium, which folds inward to generate a bilayered optic cup. During these early morphogenetic events, the optic vesicle is patterned along three different axes—proximo-distal, dorso-ventral, and naso-temporal—and three major domains: the neural retina, the retinal pigment epithelium (RPE), and the optic stalk. These fundamental steps that enable the subsequent development of a functional eye, entail the precise coordination among genetic programs. These programs are driven by the interplay of signaling pathways and transcription factors, which progressively dictate how each tissue should evolve. Here, we discuss the contribution of the Hh, Wnt, FGF, and BMP signaling pathways to the early patterning of the retina. Comparative studies in different vertebrate species have shown that their morphogenetic activity is repetitively used to orchestrate the progressive specification of the eye with evolutionary conserved mechanisms that have been adapted to match the specific need of a given species.

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