Optic Stalk | ScienceGate

The Drosophila homeobox gene sine oculis is expressed in the rostral region of the embryo in early development and is essential for eye and brain formation. Its murine homolog, Six3, is expressed in the anterior neural plate and eye anlage, and may have crucial functions in eye and brain development. In this study, we describe the cloning and expression of zebrafish six3, the apparent ortholog of the mouse Six3 gene. Zebrafish six3 transcripts are first seen in hypoblast cells in early gastrula embryos and are found in the anterior axial mesendoderm through gastrulation. six3 expression in the head ectoderm begins at late gastrula. Throughout the segmentation period, six3 is expressed in the rostral region of the prospective forebrain. Overexpression of six3 in zebrafish embryos induced enlargement of the rostral forebrain, enhanced expression of pax2 in the optic stalk and led to a general disorganization of the brain. Disruption of either the Six domain or the homeodomain abolish these effects, implying that these domains are essential for six3 gene function. Our results suggest that the vertebrate Six3 genes are involved in the formation of the rostral forebrain.

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

Development ◽

10.1242/dev.121.10.3267 ◽

1995 ◽

Vol 121 (10) ◽

pp. 3267-3278 ◽

Cited By ~ 72

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.

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

Development ◽

10.1242/dev.125.13.2425 ◽

1998 ◽

Vol 125 (13) ◽

pp. 2425-2432 ◽

Cited By ~ 4

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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Expression of the BDNF gene in the developing visual system of the chick

Development ◽

10.1242/dev.120.6.1643 ◽

1994 ◽

Vol 120 (6) ◽

pp. 1643-1649 ◽

Cited By ~ 4

Author(s):

K.H. Herzog ◽

K. Bailey ◽

Y.A. Barde

Keyword(s):

Visual System ◽

Ganglion Cells ◽

Mrna Levels ◽

Retinal Ganglion ◽

Bdnf Gene ◽

Bdnf Mrna ◽

Optic Stalk ◽

Copy Numbers ◽

Activity Dependent

Using a sensitive and quantitative method, the mRNA levels of brain-derived neurotrophic factor (BDNF) were determined during the development of the chick visual system. Low copy numbers were detected, and BDNF was found to be expressed in the optic tectum already 2 days before the arrival of the first retinal ganglion cell axons, suggesting an early role of BDNF in tectal development. After the beginning of tectal innervation, BDNF mRNA levels markedly increased, and optic stalk transection at day 4 (which prevents subsequent tectal innervation) was found to reduce the contralateral tectal levels of BDNF mRNA. Comparable reductions were obtained after injection of tetrodotoxin into one eye, indicating that, already during the earliest stages of target encounter in the CNS, the degree of BDNF gene expression is influenced by activity-dependent mechanisms. BDNF mRNA was also detected in the retina itself and at levels comparable to those found in the tectum. Together with previous findings indicating that BDNF prevents the death of cultured chick retinal ganglion cells, these results support the idea that the tightly controlled expression of the BDNF gene might be important in the co-ordinated development of the visual system.

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AP-2α knockout mice exhibit optic cup patterning defects and failure of optic stalk morphogenesis

Human Molecular Genetics ◽

10.1093/hmg/ddq060 ◽

2010 ◽

Vol 19 (9) ◽

pp. 1791-1804 ◽

Cited By ~ 35

Author(s):

Erin A. Bassett ◽

Trevor Williams ◽

Amanda L. Zacharias ◽

Philip J. Gage ◽

Sabine Fuhrmann ◽

...

Keyword(s):

Knockout Mice ◽

Optic Stalk ◽

Optic Cup

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Inverse oculomotor responses of achiasmatic mice expressing a transfer-defective Vax1 mutant

10.1101/2020.10.20.346551 ◽

2020 ◽

Author(s):

Kwang Wook Min ◽

Namsuk Kim ◽

Jae Hoon Lee ◽

Younghoon Sung ◽

Museong Kim ◽

...

Keyword(s):

Retinal Ganglion Cells ◽

Ganglion Cells ◽

Optic Chiasm ◽

Stereoscopic Vision ◽

Retinal Ganglion ◽

Visual Responses ◽

Brain Areas ◽

Optic Stalk ◽

Intercellular Transfer ◽

Oculomotor Responses

ABSTRACTIn animals that exhibit stereoscopic visual responses, the axons of retinal ganglion cells (RGCs) connect to brain areas bilaterally by forming a commissure called the optic chiasm (OC). Ventral anterior homeobox 1 (Vax1) contributes to formation of the OC, acting endogenously in optic pathway cells and exogenously in growing RGC axons. Here, we generated Vax1AA/AA mice expressing the Vax1AA mutant, which is selectively incapable of intercellular transfer. We found that RGC axons cannot take up Vax1AA protein from Vax1AA/AA mouse optic stalk (OS) cells, of which maturation is delayed, and fail to access the midline. Consequently, RGC axons of Vax1AA/AA mice connect exclusively to ipsilateral brain areas, resulting in the loss of stereoscopic vision and the inversed oculomotor responses. Together, our study provides physiological evidence for the necessity of intercellular transfer of Vax1 and the importance of the OC in binocular visual responses.

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Visualisation of ribosomes in Drosophila axons using Ribo-BiFC

10.1101/706358 ◽

2019 ◽

Author(s):

Anand K Singh ◽

Akilu Abdullahi ◽

Matthias Soller ◽

Alexandre David ◽

Saverio Brogna

Keyword(s):

Ribosomal Proteins ◽

Neuronal Cell ◽

Growth Cones ◽

Distal Portion ◽

Bimolecular Fluorescence Complementation ◽

Improved Method ◽

80S Ribosome ◽

Optic Stalk ◽

Neuronal Cell Bodies ◽

Drosophila Cells

AbstractRates of protein synthesis and the number of translating ribosomes vary greatly between different cells in various cell states. The distribution of assembled, and potentially translating, ribosomes within cells can be visualised in Drosophila by using Bimolecular Fluorescence Complementation (BiFC) to monitor the interaction between tagged pairs of 40S and 60S ribosomal proteins (RPs) that are close neighbours across inter-subunit junctions in the assembled 80S ribosome. Here we describe transgenes that express two novel RP pairs tagged with Venus-based BiFC fragments that considerably increase the sensitivity of this technique that we termed Ribo-BiFC. This improved method should provide a convenient way of monitoring the local distribution of ribosomes in most Drosophila cells and we suggest that could be implemented in other organisms. We visualized 80S ribosomes in larval photoreceptors and in other neurons. Assembled ribosomes are most abundant in the various neuronal cell bodies, but they are also present along the lengths of axons and are concentrated in growth cones of larval and pupal photoreceptors. Surprisingly, there is relatively less puromycin incorporation in the distal portion of axons in the optic stalk, suggesting that some of the ribosomes that have started translation may not be engaged in elongation in axons that are still growing.

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

Development ◽

10.1242/dev.129.13.3161 ◽

2002 ◽

Vol 129 (13) ◽

pp. 3161-3171 ◽

Cited By ~ 1

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.

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Retinoic acid establishes ventral retinal characteristics

Development ◽

10.1242/dev.122.1.195 ◽

1996 ◽

Vol 122 (1) ◽

pp. 195-204 ◽

Cited By ~ 1

Author(s):

G.A. Hyatt ◽

E.A. Schmitt ◽

N. Marsh-Armstrong ◽

P. McCaffery ◽

U.C. Drager ◽

...

Keyword(s):

Transcription Factor ◽

Retinoic Acid ◽

Optic Nerve ◽

Normal Development ◽

Cell Content ◽

Optic Stalk ◽

Eye Field ◽

Dorsal Retina ◽

Choroid Fissure

The developing eye is known to be rich in retinoic acid (RA), and perturbations in RA levels during formation of the optic primordia, as well as RA receptor mutations, cause retinal malformations, especially in ventral eye regions. To test the hypothesis that RA plays a role in the establishment of ventral retinal characteristics, we examined several dorsal and ventral ocular markers in RA-treated zebrafish. The optic stalk represents the ventral-most region of the early eye field. During normal development, the optic stalks constrict, decreasing in width and are gradually replaced by the optic nerve. Systemic high RA levels cause an expansion in the optic stalk with an increased cell content and a patent lumen. In addition, the stalks do not constrict and persist into later stages of development indicating an enhancement of early ventral eye characteristics. Expression of the transcription factor pax[b], normally confined to the ventral retina, expands into the dorsal retina following RA treatment, whereas msh[c], normally expressed in the dorsal retinal pole, disappears. Activity of an aldehyde dehydrogenase that normally occupies the dorsal third of the retina is reduced or abolished following high systemic RA. When a localized RA source, an RA-soaked bead, is placed next to the developing eye, a fissure resembling the choroid fissure appears in the eye facing the bead. Taken together, these observations suggest that RA is involved in the determination of the ventral retina.

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Patterning the Vertebrate Retina with Morphogenetic Signaling Pathways

The Neuroscientist ◽

10.1177/1073858419874016 ◽

2019 ◽

Vol 26 (2) ◽

pp. 185-196 ◽

Cited By ~ 7

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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