Brn3a-Expressing Retinal Ganglion Cells Project Specifically to Thalamocortical and Collicular Visual Pathways

Quina, Lely A.; Pak, Winnie; Lanier, Jason; Banwait, Premilla; Gratwick, Kevin; Liu, Ying; Velasquez, Tomoko; O’Leary, Dennis D.M.; Goulding, Martyn; Turner, Eric E.

doi:10.1523/jneurosci.2837-05.2005

Cited by 156 publications

(152 citation statements)

References 39 publications

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“…At this developmental stage, RGCs have already been born, 56 and most of them express Brn3a. 57 This analysis confirmed previous results indicating that a proportion of mouse RGCs are tetraploid. 37 In contrast, no Brn3a-positive neurons were observed showing DNA contents higher than 4C in both wild-type and p27 Kip1¡/¡ retinas (Fig.…”

Section: Resultssupporting

confidence: 90%

“…This antibody was used at 1/1,000 for immunohistochemistry and 1/500 for immunocytochemistry. The mouse mAb against Brn3a MAB1585 (Millipore), which specifically recognizes a subpopulation of RGCs in both chick 54 and mouse 57 retinas, was diluted 1/500 for immunohistochemistry and 1/300 for flow cytometry. The rabbit poylclonal antibody against NeuN ABN78 (Millipore) was used at 1/1,000 dilution for immunohistochemistry.…”

Section: Antibodiesmentioning

confidence: 99%

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p27^Kip1participates in the regulation of endoreplication in differentiating chick retinal ganglion cells

Ovejero‐Benito

Frade

2015

Cell Cycle

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Nuclear DNA duplication in the absence of cell division (i.e. endoreplication) leads to somatic polyploidy in eukaryotic cells. In contrast to some invertebrate neurons, whose nuclei may contain up to 200,000-fold the normal haploid DNA amount (C), polyploid neurons in higher vertebrates show only 4C DNA content. To explore the mechanism that prevents extra rounds of DNA synthesis in these latter cells we focused on the chick retina, where a population of tetraploid retinal ganglion cells (RGCs) has been described. We show that differentiating chick RGCs that express the neurotrophic receptors p75 and TrkB while lacking retinoblastoma protein, a feature of tetraploid RGCs, also express p27 Kip1 . Two different short hairpin RNAs (shRNA) that significantly downregulate p27 Kip1 expression facilitated DNA synthesis and increased ploidy in isolated chick RGCs. Moreover, this forced DNA synthesis could not be prevented by Cdk4/6 inhibition, thus suggesting that it is triggered by a mechanism similar to endoreplication. In contrast, p27 Kip1 deficiency in mouse RGCs does not lead to increased ploidy despite previous observations have shown ectopic DNA synthesis in RGCs from p27 Kip1¡/¡ mice. This suggests that a differential mechanism is used for the regulation of neuronal endoreplication in mammalian versus avian RGCs.

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Section: Resultssupporting

confidence: 90%

Section: Antibodiesmentioning

confidence: 99%

p27^Kip1participates in the regulation of endoreplication in differentiating chick retinal ganglion cells

Ovejero‐Benito

Frade

2015

Cell Cycle

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“…The generation of Tlx1 and Tlx3 mutant mice, Lbx1 mutant mice, FLPe deleter mice, and Brn3a mutant mice has been described previously (Roberts et al, 1994;Rodriguez et al, 2000;Shirasawa et al, 2000;Gross et al, 2002;Quina et al, 2005). The generation of Tlx3…”

Section: Methodsmentioning

confidence: 99%

Tlx1 and Tlx3 Coordinate Specification of Dorsal Horn Pain-Modulatory Peptidergic Neurons

Xu¹,

Lopes²,

Qian³

et al. 2008

J. Neurosci.

113

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The dorsal spinal cord synthesizes a variety of neuropeptides that modulate the transmission of nociceptive sensory information. Here, we used genetic fate mapping to show that Tlx3 ϩ spinal cord neurons and their derivatives represent a heterogeneous population of neurons, marked by partially overlapping expression of a set of neuropeptide genes, including those encoding the anti-opioid peptide cholecystokinin, pronociceptive Substance P (SP), Neurokinin B, and a late wave of somatostatin. Mutations of Tlx3 and Tlx1 result in a loss of expression of these peptide genes. Brn3a, a homeobox transcription factor, the expression of which is partly dependent on Tlx3, is required specifically for the early wave of SP expression. These studies suggest that Tlx1 and Tlx3 operate high in the regulatory hierarchy that coordinates specification of dorsal horn pain-modulatory peptidergic neurons.

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“…Brn3a is specifically expressed in RGCs, and antibodies against this transcription factor are considered a reliable marker to identify and quantify RGCs. 35 Confocal microscopy images of retinal flat mounts ( Figure 1D) and cross-sections ( Figure 1E) from SNCGCatCh-GFP retinas showed strong GFP expression in RGCs and this expression was highly co-localized with the Brn3a labeling. No expression was noted in deeper retinal layers and in ChAT-positive amacrine cells of the RGC layer ( Figure S2).…”

Section: Strong Rgc-specific Expression In the Mouse Retina By A Newmentioning

confidence: 97%

“…The minor percentage of Brn3a-negative but GFP-positive cells might belong to a class of RGCs of the accessory optic, pretectal, or hypothalamic pathways that do not stain with Brn3a. 35 …”

Section: Strong Rgc-specific Expression In the Mouse Retina By A Newmentioning

confidence: 99%

A New Promoter Allows Optogenetic Vision Restoration with Enhanced Sensitivity in Macaque Retina

et al. 2017

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The majority of inherited retinal degenerations converge on the phenotype of photoreceptor cell death. Second-and third-order neurons are spared in these diseases, making it possible to restore retinal light responses using optogenetics. Viral expression of channelrhodopsin in the third-order neurons under ubiquitous promoters was previously shown to restore visual function, albeit at light intensities above illumination safety thresholds. Here, we report (to our knowledge, for the first time) activation of macaque retinas, up to 6 months post-injection, using channelrhodopsin-Ca 2+ -permeable channelrhodopsin (CatCh) at safe light intensities. High-level CatCh expression was achieved due to a new promoter based on the regulatory region of the gamma-synuclein gene (SNCG) allowing strong expression in ganglion cells across species. Our promoter, in combination with clinically proven adeno-associated virus 2 (AAV2), provides CatCh expression in peri-foveolar ganglion cells responding robustly to light under the illumination safety thresholds for the human eye. On the contrary, the threshold of activation and the proportion of unresponsive cells were much higher when a ubiquitous promoter (cytomegalovirus [CMV]) was used to express CatCh. The results of our study suggest that the inclusion of optimized promoters is key in the path to clinical translation of optogenetics.

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Brn3a-Expressing Retinal Ganglion Cells Project Specifically to Thalamocortical and Collicular Visual Pathways

Abstract: Retinal ganglion cells (RGCs

Cited by 156 publications

References 39 publications

p27^Kip1participates in the regulation of endoreplication in differentiating chick retinal ganglion cells

p27^Kip1participates in the regulation of endoreplication in differentiating chick retinal ganglion cells

Tlx1 and Tlx3 Coordinate Specification of Dorsal Horn Pain-Modulatory Peptidergic Neurons

A New Promoter Allows Optogenetic Vision Restoration with Enhanced Sensitivity in Macaque Retina

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Brn3a-Expressing Retinal Ganglion Cells Project Specifically to Thalamocortical and Collicular Visual Pathways

Abstract: Retinal ganglion cells (RGCs

Cited by 156 publications

References 39 publications

p27Kip1participates in the regulation of endoreplication in differentiating chick retinal ganglion cells

p27Kip1participates in the regulation of endoreplication in differentiating chick retinal ganglion cells

Tlx1 and Tlx3 Coordinate Specification of Dorsal Horn Pain-Modulatory Peptidergic Neurons

A New Promoter Allows Optogenetic Vision Restoration with Enhanced Sensitivity in Macaque Retina

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p27^Kip1participates in the regulation of endoreplication in differentiating chick retinal ganglion cells

p27^Kip1participates in the regulation of endoreplication in differentiating chick retinal ganglion cells