Eph Family Receptors and Their Ligands Distribute in Opposing Gradients in the Developing Mouse Retina

Marcus, Riva C.; Gale, Nicholas W.; Morrison, Mary E.; Mason, Carol A.; Yancopouloš, George D.

doi:10.1006/dbio.1996.0347

Cited by 129 publications

(97 citation statements)

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“…We investigated ephrinA5 protein expression in the retina and detected a high expression in the nasal part compared to the temporal one. This result is in accordance with the previously described retinal ephrinA5 expression pattern in the chick [51] and with ephrinA5 mRNA expression found in a high-nasal-to-low-temporal gradient in the developing mouse embryo retina [52]. As previously described, the mouse retinal ganglion cells also expressed EphA5 and EphA6 receptors [53].…”

Section: Discussionsupporting

confidence: 92%

EphrinA5 protein distribution in the developing mouse brain

Deschamps¹,

Morel²,

Janet³

et al. 2010

BMC Neurosci

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Background EphrinA5 is one of the best-studied members of the Eph-ephrin family of guidance molecules, known to be involved in brain developmental processes. Using in situ hybridization, ephrinA5 mRNA expression has been detected in the retinotectal, the thalamocortical, and the olfactory systems; however, no study focused on the distribution of the protein. Considering that this membrane-anchored molecule may act far from the neuron soma expressing the transcript, it is of a crucial interest to localize ephrinA5 protein to better understand its function. Results Using immunohistochemistry, we found that ephrinA5 protein is highly expressed in the developing mouse brain from E12.5 to E16.5. The olfactory bulb, the cortex, the striatum, the thalamus, and the colliculi showed high intensity of labelling, suggesting its implication in topographic mapping of olfactory, retinocollicular, thalamocortical, corticothalamic and mesostriatal systems. In the olfactory nerve, we found an early ephrinA5 protein expression at E12.5 suggesting its implication in the guidance of primary olfactory neurons into the olfactory bulb. In the thalamus, we detected a dynamic graduated protein expression, suggesting its role in the corticothalamic patterning, whereas ephrinA5 protein expression in the target region of mesencephalic dopaminergic neurones indicated its involvement in the mesostriatal topographic mapping. Following E16.5, the signal faded gradually and was barely detectable at P0, suggesting a main role for ephrinA5 in primary molecular events in topographic map formation. Conclusion Our work shows that ephrinA5 protein is expressed in restrictive regions of the developing mouse brain. This expression pattern points out the potential sites of action of this molecule in the olfactory, retinotectal, thalamocortical, corticothalamic and mesostriatal systems, during development. This study is essential to better understand the role of ephrinA5 during developmental topographic mapping of connections and to further characterise the mechanisms involved in pathway restoration following cell transplantation in the damaged brain.

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Section: Discussionsupporting

confidence: 92%

EphrinA5 protein distribution in the developing mouse brain

Deschamps¹,

Morel²,

Janet³

et al. 2010

BMC Neurosci

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“…The pattern suggests that unknown retinal molecule(s) with peripheral to central gradients of distribution may be defective or modify photoreceptor degeneration in RP. Although intraretinal gradients of various molecules are present during development and postnatally (van Ginkel et al, 1995;Marcus et al, 1996;McCaffery et al, 1999;Schulte et al, 1999;Gru È n et al, 2000;Mic et al, 2000;Suzuki et al, 2000), to the authors' knowledge none of these gradients match the pattern of photoreceptor death found in concentric RP. Rather, the opposite is true for the distribution of one known photoreceptor survival factor, basic ®broblast growth factor, which is highest in rods in the far periphery and lowest in rods in the macula (Li, Chang and Milam, 1997).…”

Section: Discussionmentioning

confidence: 96%

Concentric Retinitis Pigmentosa: Clinicopathologic Correlations

Milam

Castro

Smith

et al. 2001

Experimental Eye Research

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Progressive concentric (centripetal) loss of vision is one pattern of visual ®eld loss in retinitis pigmentosa. This study provides the ®rst clinicopathologic correlations for this form of retinitis pigmentosa. A family with autosomal dominant concentric retinitis pigmentosa was examined clinically and with visual function tests. A post-mortem eye of an affected 94 year old family member was processed for histopathology and immunocytochemistry with retinal cell speci®c antibodies. Unrelated simplex/ multiplex patients with concentric retinitis pigmentosa were also examined. Affected family members of the eye donor and patients from the other families had prominent peripheral pigmentary retinopathy with more normal appearing central retina, good visual acuity, concentric ®eld loss, normal or near normal rod and cone sensitivity within the preserved visual ®eld, and reduced rod and cone electroretinograms. The eye donor, at age 90, had good acuity and function in a central island. Grossly, the central region of the donor retina appeared thinned but otherwise normal, while the far periphery contained heavy bone spicule pigment. Microscopically the central retina showed photoreceptor outer segment shortening and some photoreceptor cell loss. The mid periphery had a sharp line of demarcation where more central photoreceptors were near normal except for very short outer segments and peripheral photoreceptors were absent. Rods and cones showed abrupt loss of outer segments and cell death at this interface. It is concluded that concentric retinitis pigmentosa is a rare but recognizable phenotype with slowly progressive photoreceptor death from the far periphery toward the central retina. The disease is retina-wide but shows regional variation in severity of degeneration; photoreceptor death is severe in the peripheral retina with an abrupt edge between viable and degenerate photoreceptors. Peripheral to central gradients of unknown retinal molecule(s) may be defective or modify photoreceptor degeneration in concentric retinitis pigmentosa.

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“…These data support a role for ALDHs in retinal compartmentalization and patterning and suggest that RA may serve as a position-specific tag involved in guiding retinal axons to their correct targets in the brain (12,16,17). Because ALDH1 is expressed at early stages of retinal development, prior to axon formation, asymmetry in RA levels may be required to mark the different axes of the retina and to form the basis for retinotectal organization, as previously suggested for some Eph receptors and their ephrin ligands (18,19).…”

Section: From the Department Of Oncology University Of Alberta And Cmentioning

confidence: 80%

Differential Regulation of the Aldehyde Dehydrogenase 1 Gene in Embryonic Chick Retina and Liver

Godbout

Monckton

2001

Journal of Biological Chemistry

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Aldehyde dehydrogenase (ALDH1) is highly expressed in the dorsal cells of the undifferentiated retina, where it has been proposed to play a role in the formation of a retinoic acid gradient along the ventrodorsal axis. In contrast to the retina, ALDH1 levels increase with differentiation in the liver and remain elevated in the adult tissue. To understand the molecular basis for differential expression of ALDH1 during development, we characterized the ALDH1 transcripts expressed in chick retina and liver. By sequencing, primer extension, and S1 nuclease analysis, we show that retina ALDH1 mRNA has an additional 300 nucleotides of 5-untranslated sequence resulting from the transcription of two 5 noncoding exons. There is a 24 -29-kilobase pair (kb) gap between exons 1 and 2 and a 290-base pair gap between exons 2 and 3. Exon 3, which contains the ALDH1 start codon, represents the first exon of the liver transcript. Using a reporter gene assay, we have identified tissuespecific regulatory elements that govern ALDH1 expression in primary retina and liver cultures. Constructs with >1.6 kb of DNA flanking the 5-end of exon 1 showed elevated activity in retinal cultures but only basal activity in liver cultures. In contrast, constructs with <1 kb of 5-flanking DNA were active in both retina and liver cultures. Our results suggest that an important mechanism for the control of ALDH1 transcriptional activity is through the presence of inhibitory elements located 0.7-1.6 kb upstream of the ALDH1 gene. DNase I footprint analysis reveal four sites of protein-DNA interaction within this region, one of which is specific to the liver and corresponds to a NF-B/Rel binding site.

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Eph Family Receptors and Their Ligands Distribute in Opposing Gradients in the Developing Mouse Retina

Cited by 129 publications

References 0 publications

EphrinA5 protein distribution in the developing mouse brain

EphrinA5 protein distribution in the developing mouse brain

Concentric Retinitis Pigmentosa: Clinicopathologic Correlations

Differential Regulation of the Aldehyde Dehydrogenase 1 Gene in Embryonic Chick Retina and Liver

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