The role of Pax-6 in eye and nasal development

Development ◽  
1995 ◽  
Vol 121 (5) ◽  
pp. 1433-1442 ◽  
Author(s):  
J.C. Grindley ◽  
D.R. Davidson ◽  
R.E. Hill
Keyword(s):  
Mrna Expression ◽  
Optic Vesicle ◽  
Surface Ectoderm ◽  
Nasal Cavities ◽  
Optic Vesicles ◽  
Neural Ectoderm ◽  
Nasal Region ◽  
Nasal Development ◽  
Or Genes ◽  
Lens Placode

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.

Mechanics of Optic Cup Invagination in the Embryonic Chick Eye

2012 ◽  
Author(s):  
Alina Oltean ◽  
David C. Beebe ◽  
Larry A. Taber
Keyword(s):  
Eye Development ◽  
Embryonic Chick ◽  
Optic Vesicle ◽  
Surface Ectoderm ◽  
Morphogenetic Process ◽  
Optic Cup ◽  
Optic Vesicles ◽  
Lens Vesicle ◽  
Lens Placode

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].

Different roles for Pax6 in the optic vesicle and facial epithelium mediate early morphogenesis of the murine eye

Development ◽  
2000 ◽  
Vol 127 (5) ◽  
pp. 945-956 ◽  
Author(s):  
J.M. Collinson ◽  
R.E. Hill ◽  
J.D. West
Keyword(s):  
Histological Analysis ◽  
Eye Development ◽  
Wild Type Mouse ◽  
Lens Epithelium ◽  
Optic Vesicle ◽  
Wild Type ◽  
Adhesive Properties ◽  
Optic Vesicles ◽  
Lens Placode ◽  
Mutant Cells

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.

FGF1 patterns the optic vesicle by directing the placement of the neural retina domain

Development ◽  
1998 ◽  
Vol 125 (5) ◽  
pp. 869-877 ◽  
Author(s):  
J. Hyer ◽  
T. Mima ◽  
T. Mikawa
Keyword(s):  
Neural Retina ◽  
Expression Vectors ◽  
Expression Data ◽  
Optic Vesicle ◽  
Surface Ectoderm ◽  
Pigmented Epithelium ◽  
Optic Vesicles ◽  
Cell Phenotypes

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.

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.

The upstream ectoderm enhancer in Pax6 has an important role in lens induction

Development ◽  
2001 ◽  
Vol 128 (22) ◽  
pp. 4415-4424 ◽  
Author(s):  
Patricia V. Dimanlig ◽  
Sonya C. Faber ◽  
Woytek Auerbach ◽  
Helen P. Makarenkova ◽  
Richard A. Lang
Keyword(s):  
Transcriptional Control ◽  
Control Element ◽  
Pax6 Gene ◽  
Pax6 Expression ◽  
Surface Ectoderm ◽  
Targeted Deletion ◽  
Lens Vesicle ◽  
Normal Lens ◽  
Lens Formation ◽  
Lens Placode

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.

Is there a ventral neural ridge in chick embryos? Implications for the origin of adenohypophyseal and other APUD cells

Development ◽  
1980 ◽  
Vol 57 (1) ◽  
pp. 71-78
Author(s):  
N. B. Levy ◽  
Ann Andrew ◽  
B. B. Rawdon ◽  
Beverley Kramer
Keyword(s):  
Neural Crest ◽  
Endocrine Cells ◽  
Ventral Surface ◽  
Neural Plate ◽  
Chick Embryos ◽  
Serial Sections ◽  
Apud Cells ◽  
Surface Ectoderm ◽  
Neural Ectoderm ◽  
Thickened Surface

Two- to ten-somite chick embryos were studied in order to ascertain whether, as has been proposed, there exists a ‘ventral neural ridge’ which gives rise to the hypophyseal (Rathke's) pouch. Serial sections and stereo-microscopy were used. The neural ridges arch around the rostral end of the embryo onto the ventral surface of the head, but no evidence was found for their extension to form a ‘ventral neural ridge’ reaching the stomodaeum: in fact a considerable expanse of non-thickened surface ectoderm was seen to separate the ventral portions of the neural ridges from the stomodaeum. The thickening of neural ectoderm which does appear on the ventral surface of the head results from apposition and fusion of the opposite neural ridges flanking the neural plate and thus the tip of the anterior neuropore - the classically accepted mode of closure of the neuropore. These findings are in accord with the generally accepted concept of the origin of thehypophyseal pouch rather than with its derivation from a ‘ventral neural ridge’. No sign of neural crest formation was encountered ventrally; this observation excludes the possibility that endocrine cells of the APUD series could originate from neural crest in this region.

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 Mechanical effects of the surface ectoderm on optic vesicle morphogenesis in the chick embryo

2014 ◽  
Vol 47 (16) ◽  
pp. 3837-3846 ◽  
Author(s):  
Hadi S. Hosseini ◽  
David C. Beebe ◽  
Larry A. Taber
Keyword(s):  
Chick Embryo ◽  
Optic Vesicle ◽  
Surface Ectoderm ◽  
Mechanical Effects

Signaling and transcriptional regulation in early mammalian eye development: a link between FGF and MITF

Development ◽  
2000 ◽  
Vol 127 (16) ◽  
pp. 3581-3591 ◽  
Author(s):  
M. Nguyen ◽  
H. Arnheiter
Keyword(s):  
Gene Expression ◽  
Transcription Factor ◽  
Transcription Factors ◽  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Pigment Epithelium ◽  
Fibroblast Growth ◽  
Optic Vesicle ◽  
Surface Ectoderm ◽  
Pigmented Epithelium

During vertebrate eye development, the optic vesicle is partitioned into a domain at its distal tip that will give rise to the neuroretina, and another at its proximal base that will give rise to the pigmented epithelium. Both domains are initially bipotential, each capable of giving rise to either neuroretina or pigmented epithelium. The partitioning depends on extrinsic signals, notably fibroblast growth factors, which emanate from the overlying surface ectoderm and induce the adjacent neuroepithelium to assume the neuroretinal fate. Using explant cultures of mouse optic vesicles, we demonstrate that bipotentiality of the optic neuroepithelium is associated with the initial coexpression of the basic-helix-loop-helix-zipper transcription factor MITF, which is later needed solely in the pigmented epithelium, and a set of distinct transcription factors that become restricted to the neuroretina. Implantation of fibroblast growth factor-coated beads close to the base of the optic vesicle leads to a rapid downregulation of MITF and the development of an epithelium that, by morphology, gene expression, and lack of pigmentation, resembles the future neuroretina. Conversely, the removal of the surface ectoderm results in the maintenance of MITF in the distal optic epithelium, lack of expression of the neuroretinal-specific CHX10 transcription factor, and conversion of this epithelium into a pigmented monolayer. This phenomenon can be prevented by the application of fibroblast growth factor alone. In Mitf mutant embryos, parts of the future pigment epithelium become thickened, lose expression of a number of pigment epithelium transcription factors, gain expression of neuroretinal transcription factors, and eventually transdifferentiate into a laminated second retina. The results support the view that the bipotential optic neuroepithelium is characterized by overlapping gene expression patterns and that selective gene repression, brought about by local extrinsic signals, leads to the separation into discrete expression domains and, hence, to domain specification.

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