Mechanics of Optic Cup Invagination in the Embryonic Chick Eye

Author(s):  
Alina Oltean ◽  
David C. Beebe ◽  
Larry A. Taber

Invagination of epithelia is an essential morphogenetic process that occurs in early eye development. The mechanics of the tissue forces necessary for eye invagination are not yet understood [1]. The eyes begin as two optic vesicles that grow outwards from the forebrain and adhere to the surface ectoderm. At this point of contact, both the surface ectoderm and optic vesicle thicken, forming the lens placode and retinal placode, respectively. The two placodes then bend inward to create the lens vesicle and bilayered optic cup (OC) [1, 2].

Development ◽  
2000 ◽  
Vol 127 (5) ◽  
pp. 945-956 ◽  
Author(s):  
J.M. Collinson ◽  
R.E. Hill ◽  
J.D. West

Chimaeric mice were made by aggregating Pax6(−/−) and wild-type mouse embryos, in order to study the interaction between the optic vesicle and the prospective lens epithelium during early stages of eye development. Histological analysis of the distribution of homozygous mutant cells in the chimaeras showed that the cell-autonomous removal of Pax6(−/−) cells from the lens, shown previously at E12.5, is nearly complete by E9.5. Most mutant cells are eliminated from an area of facial epithelium wider than, but including, the developing lens placode. This result suggests a role for Pax6 in maintaining a region of the facial epithelium that has the tissue competence to undergo lens differentiation. Segregation of wild-type and Pax6(−/−) cells occurs in the optic vesicle at E9.5 and is most likely a result of different adhesive properties of wild-type and mutant cells. Also, proximo-distal specification of the optic vesicle (as assayed by the elimination of Pax6(−/−) cells distally), is disrupted in the presence of a high proportion of mutant cells. This suggests that Pax6 operates during the establishment of patterning along the proximo-distal axis of the vesicle. Examination of chimaeras with a high proportion of mutant cells showed that Pax6 is required in the optic vesicle for maintenance of contact with the overlying lens epithelium. This may explain why Pax6(−/−) optic vesicles are inefficient at inducing a lens placode. Contact is preferentially maintained when the lens epithelium is also wild-type. Together, these results demonstrate requirements for functional Pax6 in both the optic vesicle and surface epithelia in order to mediate the interactions between the two tissues during the earliest stages of eye development.


Development ◽  
1995 ◽  
Vol 121 (5) ◽  
pp. 1433-1442 ◽  
Author(s):  
J.C. Grindley ◽  
D.R. Davidson ◽  
R.E. Hill

Small eye (Sey) mice homozygous for mutations in the Pax-6 gene have no lenses and no nasal cavities. We have examined the ontogeny of eye and nasal defects in Sey/Sey embryos and have related the defects seen to the pattern of Pax-6 mRNA expression in the mouse during normal eye and nasal development. There are two principal components of the early eye, the neural ectoderm of the optic vesicle, which forms the retina, and the overlying surface ectoderm, which forms the lens and cornea. By studying these interacting tissues in normal and Sey/Sey embryos, we have identified processes for which Pax-6 is important and can thus suggest possible roles for the Pax-6 gene. Pax-6 is essential for the formation of lens placodes from surface ectoderm. In normal development, early Pax-6 mRNA expression in a broad domain of surface ectoderm is downregulated, but expression is specifically maintained in the developing lens placode. Moreover, other Pax-6-expressing tissues are frequently those that have can transdifferentiate into lens. Thus, phenotype and expression together suggest a role for Pax-6 in lens determination. At least some functions of Pax-6 can be separated from the influence of other tissues. Early Sey/Sey optic vesicles are abnormally broad and fail to constrict proximally. These defects occur prior to the time of lens placode formation and probably reflect a requirement for Pax-6 in neural ectoderm. In surface ectoderm domains, where Pax-6 expression is known to be independent of the presence of an optic vesicle, Pax-6 function is required for the maintenance of its own transcription. The mutual dependency of lens and optic vesicle development can also be studied using the Small eye mutation. Using region-specific markers we find that, in the morphologically abnormal Sey/Sey optic vesicles, aspects of normal proximo-distal specification nevertheless persist, despite the complete absence of lens. Like the lens, the nasal cavities develop from ectodermal placodes that normally express Pax-6 mRNA, fail to form in Sey/Sey mice and show Pax-6-dependent Pax-6 mRNA regulation. Analysis of patterns of programmed cell death and absence of nasal region expression from an Msx-1 transgene in Sey/Sey embryos suggest a requirement for Pax-6 in the transition from presumptive nasal ectoderm to placode, and that Msx-1, or genes regulating it, are possible targets for Pax-6.


Development ◽  
2000 ◽  
Vol 127 (21) ◽  
pp. 4599-4609 ◽  
Author(s):  
S. Fuhrmann ◽  
E.M. Levine ◽  
T.A. Reh

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.


Development ◽  
2001 ◽  
Vol 128 (22) ◽  
pp. 4415-4424 ◽  
Author(s):  
Patricia V. Dimanlig ◽  
Sonya C. Faber ◽  
Woytek Auerbach ◽  
Helen P. Makarenkova ◽  
Richard A. Lang

The Pax6 gene has a central role in development of the eye. We show, through targeted deletion in the mouse, that an ectoderm enhancer in the Pax6 gene is required for normal lens formation. Ectoderm enhancer-deficient embryos exhibit distinctive defects at every stage of lens development. These include a thinner lens placode, reduced placodal cell proliferation, and a small lens pit and lens vesicle. In addition, the lens vesicle fails to separate from the surface ectoderm and the maturing lens is smaller and shows a delay in fiber cell differentiation. Interestingly, deletion of the ectoderm enhancer does not eliminate Pax6 production in the lens placode but results in a diminished level that, in central sections, is apparent primarily on the nasal side. This argues that Pax6 expression in the lens placode is controlled by the ectoderm enhancer and at least one other transcriptional control element. It also suggests that Pax6 enhancers active in the lens placode drive expression in distinct subdomains, an assertion that is supported by the expression pattern of a lacZ reporter transgene driven by the ectoderm enhancer. Interestingly, deletion of the ectoderm enhancer causes loss of expression of Foxe3, a transcription factor gene mutated in the dysgenetic lens mouse. When combined, these data and previously published work allow us to assemble a more complete genetic pathway describing lens induction. This pathway features (1) a pre-placodal phase of Pax6 expression that is required for the activity of multiple, downstream Pax6 enhancers; (2) a later, placodal phase of Pax6 expression regulated by multiple enhancers; and (3) the Foxe3 gene in a downstream position. This pathway forms a basis for future analysis of lens induction mechanism.


Development ◽  
1991 ◽  
Vol 112 (4) ◽  
pp. 1053-1061 ◽  
Author(s):  
A.P. Monaghan ◽  
D.R. Davidson ◽  
C. Sime ◽  
E. Graham ◽  
R. Baldock ◽  
...  

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.


eLife ◽  
2015 ◽  
Vol 4 ◽  
Author(s):  
Stephan Heermann ◽  
Lucas Schütz ◽  
Steffen Lemke ◽  
Kerstin Krieglstein ◽  
Joachim Wittbrodt

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.


1988 ◽  
Vol 9 (7) ◽  
pp. 227-233
Author(s):  
Joseph H. Calhoun

A cataract is a loss of transparency of any size or degree in that unique organ of vision, the crystalline lens of the eye. To the layman a cataract often connotes a visually significant opacity that impairs vision and requires surgery. ANATOMY OF THE LENS The lens is a biconcave transparent organ that can alter its shape to meet different optical needs. It lies immediately posterior to the iris and just anterior to the vitreous humor. A portion of the lens is visible through the pupil. The lens is held or suspended in place by the zonules or suspensory ligaments, which arise from the reqion of the ciliary processes and attach to the equator of the lens. EMBRYOLOGY OF THE LENS The lens is unique in many ways. At about the 4-mm stage in the embroy. the surface ectoderm over the advancing optic vesicle begins to thicken, and then invaginates to form the lens pit, which later separates from the surface ectoderm to form a spherical cavity, the lens vesicle. Those cells originally on the surface of the ectoderm now line the lens vesicle surrounded by the basement membrane of these cells, the future lens capsule. By the seventh week of life, those cells on the posterior part of the vesicle have elongated and proliferated to obliterate the cavity of the lens vesicle to form the embryonic nucleus, which remains unchanged throughout life (Fig 1).


Development ◽  
1998 ◽  
Vol 125 (5) ◽  
pp. 869-877 ◽  
Author(s):  
J. Hyer ◽  
T. Mima ◽  
T. Mikawa

Patterning of the bipotential retinal primordia (the optic vesicles) into neural retina and retinal pigmented epithelium depends on its interaction with overlaying surface ectoderm. The surface ectoderm expresses FGFs and the optic vesicles express FGF receptors. Previous FGF-expression data and in vitro analyses support the hypothesis that FGF signaling plays a significant role in patterning the optic vesicle. To test this hypothesis in vivo we removed surface ectoderm, a rich source of FGFs. This ablation generated retinas in which neural and pigmented cell phenotypes were co-mingled. Two in vivo protocols were used to replace FGF secretion by surface ectoderm: (1) implantation of FGF-secreting fibroblasts, and (2) injection of replication-incompetent FGF retroviral expression vectors. The retinas in such embryos exhibited segregated neural and pigmented epithelial domains. The neural retina domains were always close to a source of FGF secretion. These results indicate that, in the absense of surface ectoderm, cells of the optic vesicles display both neural and pigmented retinal phenotypes, and that positional cues provided by FGF organize the bipotential optic vesicle into specific neural retina and pigmented epithelium domains. We conclude that FGF can mimic one of the earliest functions of surface ectoderm during eye development, namely the demarcation of neural retina from pigmented epithelium.


Development ◽  
1998 ◽  
Vol 125 (13) ◽  
pp. 2425-2432 ◽  
Author(s):  
T. Hollemann ◽  
E. Bellefroid ◽  
T. Pieler

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.


Development ◽  
2002 ◽  
Vol 129 (19) ◽  
pp. 4535-4545 ◽  
Author(s):  
Nicole Bäumer ◽  
Till Marquardt ◽  
Anastassia Stoykova ◽  
Ruth Ashery-Padan ◽  
Kamal Chowdhury ◽  
...  

The establishment of polarity is an important step during organ development. We assign a function for the paired and homeodomain transcription factor Pax6 in axis formation in the retina. Pax6 is a key factor of the highly conserved genetic network implicated in directing the initial phases of eye development. We recently demonstrated that Pax6 is also essential for later aspects of eye development, such as lens formation and retinogenesis. In this study, we present evidence that a highly conserved intronic enhancer, α, in the Pax6 gene is essential for the establishment of a distalhigh-proximallow gradient of Pax6 activity in the retina. In the mature retina, the activity mediated by the α-enhancer defines a population of retinal ganglion cells that project to two sickle-shaped domains in the superior colliculus and lateral geniculate nucleus. Deletion of the α-enhancer in vivo revealed that retinal Pax6 expression is regulated in two complementary topographic domains. We found that Pax6 activity is required for the establishment, as well as the maintenance of dorsal and nasotemporal characteristics in the optic vesicle and, later, the optic cup.


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