Midline signalling is required for Pax gene regulation and patterning of the eyes

Development ◽  
1995 ◽  
Vol 121 (10) ◽  
pp. 3267-3278 ◽  
Author(s):  
R. Macdonald ◽  
K.A. Barth ◽  
Q. Xu ◽  
N. Holder ◽  
I. Mikkola ◽  
...  
Keyword(s):  
Developmental Stages ◽  
Pigment Epithelium ◽  
Neural Retina ◽  
Protein Distribution ◽  
Optic Stalk ◽  
Retinal Tissue ◽  
Pax6 Protein ◽  
Signalling Molecule ◽  
Pax Family ◽  
In Cells

Pax6 and Pax2 are members of the Pax family of transcription factors that are both expressed in the developing visual system of zebrafish embryos. Pax6 protein is present in all cells that form the neural retina and pigment epithelium, whereas Pax2 is located primarily in cells that will give rise to the optic stalk. In this study, we have addressed the role of midline signalling in the regulation of Pax2 and Pax6 distributions and in the subsequent morphogenesis of the eyes. Midline signalling is severely perturbed in cyclops mutant embryos resulting in an absence of ventral midline CNS tissue and fusion of the eyes. Mutant embryos ectopically express Pax6 in a bridge of tissue around the anterior pole of the neural keel in the position normally occupied by cells that form the optic stalks. In contrast, Pax2 protein is almost completely absent from this region in mutant embryos. Concommitant with the changes in Pax protein distribution, cells in the position of the optic stalks differentiate as retina. These results suggest that a signal emanating from the midline, which is absent in cyclops mutant embryos, may be required to promote Pax2 and inhibit Pax6 expression in cells destined to form the optic stalks. Sonic hedgehog (Shh also known as Vhh-1 and Hhg-1) is a midline signalling molecule that is absent from the neuroepithelium of cyclops mutant embryos at early developmental stages. To test the possibility that Shh might be able to regulate the spatial expression of Pax6 and Pax2 in the optic primordia, it was overexpressed in the developing CNS. The number of cells containing Pax2 was increased following shh overexpression and embryos developed hypertrophied optic stalk-like structures. Complimentary to the changes in Pax2 distribution, there were fewer Pax6-containing cells and pigment epithelium and neural retina were reduced. Our results suggest that Shh or a closely related signalling molecule emanating from midline tissue in the ventral forebrain either directly or indirectly induces the expression of Pax2 and inhibits the expression of Pax6 and thus may regulate the partitioning of the optic primordia into optic stalks and retinal tissue.

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.

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.

scholarly journals Otx genes are required for tissue specification in the developing eye

Development ◽  
2001 ◽  
Vol 128 (11) ◽  
pp. 2019-2030 ◽  
Author(s):  
Juan Ramon Martinez-Morales ◽  
Massimo Signore ◽  
Dario Acampora ◽  
Antonio Simeone ◽  
Paola Bovolenta
Keyword(s):  
Apoptotic Cell ◽  
Pigment Epithelium ◽  
Neural Retina ◽  
Dependent Manner ◽  
Gene Products ◽  
Optic Stalk ◽  
Mutual Regulation ◽  
Vertebrate Eye ◽  
Dose Dependent

Patterning of the vertebrate eye appears to be controlled by the mutual regulation and the progressive restriction of the expression domains of a number of genes initially co-expressed within the eye anlage. Previous data suggest that both Otx1 and Otx2 might contribute to the establishment of the different eye territories. Here, we have analysed the ocular phenotype of mice carrying different functional copies of Otx1 and Otx2 and we show that these genes are required in a dose-dependent manner for the normal development of the eye. Thus, all Otx1−/−; Otx2+/− and 30% of Otx1+/−; Otx2+/− genotypes presented consistent and profound ocular malformation, including lens, pigment epithelium, neural retina and optic stalk defects. During embryonic development, optic vesicle infolding was severely altered and the expression of pigment epithelium-specific genes, such as Mitf or tyrosinase, was lost. Lack of pigment epithelium specification was associated with an expansion of the prospective neural retina and optic stalk territories, as determined by the expression of Pax6, Six3 and Pax2. Later in development the presumptive pigment epithelium region acquired features of mature neural retina, including the generation of Islet1-positive neurones. Furthermore, in Otx1−/−; Otx2+/− mice neural retina cell proliferation, cell differentiation and apoptotic cell death were also severely affected. Based on these findings we propose a model in which Otx gene products are required for the determination and differentiation of the pigment epithelium, co-operating with other eye patterning genes in the determination of the specialised tissues that will constitute the mature vertebrate eye.

scholarly journals INTACT RETINAL TISSUE AND RETINAL PIGMENT EPITHELIUM IDENTIFIED WITHIN A COLOBOMA BY HIGH-SPEED, ULTRAHIGH-RESOLUTION OPTICAL COHERENCE TOMOGRAPHY

2011 ◽  
Vol 5 (1) ◽  
pp. 46-48 ◽  
Author(s):  
Christopher H Judson ◽  
Laurel N Vuong ◽  
Iwona Gorczynska ◽  
Vivek J Srinivasan ◽  
James G Fujimoto ◽  
...  
Keyword(s):  
Optical Coherence Tomography ◽  
Retinal Pigment Epithelium ◽  
High Speed ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Optical Coherence ◽  
Ultrahigh Resolution ◽  
Retinal Tissue

‘Transdifferentiation’ of chicken neural retina into lens and pigment epithelium in culture: controlling influences

Development ◽  
1978 ◽  
Vol 48 (1) ◽  
pp. 1-21
Author(s):  
D. J. Pritchard ◽  
R. M. Clayton ◽  
D. I. De Pomerai
Keyword(s):  
Pigment Cell ◽  
Pigment Epithelium ◽  
Neural Retina ◽  
Medium Composition ◽  
Pigment Cells ◽  
Bicarbonate Concentration ◽  
Experimental Conditions ◽  
Culture Growth ◽  
New Hypothesis

The in vitro transdifferentiation of chicken embryo neural retina into pigment epithelium and lens cells was investigated under a variety of experimental conditions. Our findings suggest that some aspects of the phenomena are a function of medium composition and volume, whereas others depend upon conditions which develop during culture growth. Before melanin is visible, potential pigment cells are recognized as foci within epithelialsheets which remain in contact with the dish. The final area occupied by colonies of potential pigment cells is directly proportional to bicarbonate concentration. Low total medium volume also favours formation of potential pigment cells. In contrast the extent of cells other than potential pigment cells is not related to bicarbonate and is favoured when the volume of medium is large. Accumulation of melanin within the potential pigment cell colonies is suppressed when cells are crowded together. Lentoid bodies are formed from cells which are distinct from potential pigment cells and arise in crowded situations, in association with multilayering. Another type of structure superficially resembling a lentoid is derived from cell aggregates formed during the initial establishment of cultures. The survival of these ‘aggregate bodies’ is inversely related to bicarbonate concentration. Crystallin content is unrelated to lentoid numbers. The results provide the basis for a new hypothesis concerning cytodifferentiation in this system.

scholarly journals Cholesterol homeostasis in the vertebrate retina: Biology and pathobiology

2020 ◽  
pp. jlr.TR120000979 ◽  
Author(s):  
Sriganesh Ramachandra Rao ◽  
Steven J. Fliesler
Keyword(s):  
De Novo ◽  
Current Knowledge ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Neural Retina ◽  
Cholesterol Homeostasis ◽  
Sterol Synthesis ◽  
Topic Area ◽  
Sterol Transport ◽  
Age Related

Cholesterol is a quantitatively and biologically significant constituent of all mammalian cell membrane, including those that comprise the retina. Retinal cholesterol homeostasis entails the interplay between de novo synthesis, uptake, intra-retinal sterol transport, metabolism and efflux. Defects in these complex processes are associated with several congenital and age-related disorders of the visual system. Herein, we provide an overview of the following topics: a) cholesterol synthesis in the neural retina; b) lipoprotein uptake and intraretinal sterol transport in the neural retina and the retinal pigment epithelium (RPE); c) cholesterol efflux from the neural retina and the RPE; and d) biology and pathobiology of defects in sterol synthesis and sterol oxidation in the neural retina and the RPE. We focus, in particular, on studies involving animal models of monogenic disorders pertinent to the above topics, as well as in vitro models using biochemical, metabolic, and omic approaches. We also identify current knowledge gaps as well as opportunities in the field that beg further research in this topic area.

scholarly journals KCNQ5/Kv7.5 potassium channel expression and subcellular localization in primate retinal pigment epithelium and neural retina

2011 ◽  
Vol 301 (5) ◽  
pp. C1017-C1026 ◽  
Author(s):  
Xiaoming Zhang ◽  
Dongli Yang ◽  
Bret A. Hughes
Keyword(s):  
Visual Information ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Basal Membrane ◽  
Cell Types ◽  
Neural Retina ◽  
Pcr Analysis ◽  
Rod Photoreceptor ◽  
Rpe Cells ◽  
Channel Expression

Previous studies identified in retinal pigment epithelial (RPE) cells an M-type K+ current, which in many other cell types is mediated by channels encoded by KCNQ genes. The aim of this study was to assess the expression of KCNQ genes in the monkey RPE and neural retina. Application of the specific KCNQ channel blocker XE991 eliminated the M-type current in freshly isolated monkey RPE cells, indicating that KCNQ subunits contribute to the underlying channels. RT-PCR analysis revealed the expression of KCNQ1, KCNQ4, and KCNQ5 transcripts in the RPE and all five KCNQ transcripts in the neural retina. At the protein level, KCNQ5 was detected in the RPE, whereas both KCNQ4 and KCNQ5 were found in neural retina. In situ hybridization in frozen monkey retinal sections revealed KCNQ5 gene expression in the ganglion cell layer and the inner and outer nuclear layers of the neural retina, but results in the RPE were inconclusive due to the presence of melanin. Immunohistochemistry revealed KCNQ5 in the inner and outer plexiform layers, in cone and rod photoreceptor inner segments, and near the basal membrane of the RPE. The data suggest that KCNQ5 channels contribute to the RPE basal membrane K+ conductance and, thus, likely play an important role in active K+ absorption. The distribution of KCNQ5 in neural retina suggests that these channels may function in the shaping of the photoresponses of cone and rod photoreceptors and the processing of visual information by retinal neurons.

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