Radial migration: Retinal neurons hold on for the ride

Newborn neuron radial migration is a key force shaping the nervous system. In this issue, Icha et al. (2016. J. Cell Biol. http://dx.doi.org/10.1083/jcb.201604095) use zebrafish retinal ganglion cells as a model to investigate the cell biological basis of radial migration and the consequences for retinal histogenesis when migration is impaired.

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Autonomic Regulation of the Eye

Oxford Research Encyclopedia of Neuroscience ◽

10.1093/acrefore/9780190264086.013.276 ◽

2019 ◽

Cited By ~ 1

Author(s):

Paul J. May ◽

Anton Reiner ◽

Paul D. Gamlin

Keyword(s):

Blood Flow ◽

Nervous System ◽

Retinal Ganglion Cells ◽

Aqueous Humor ◽

Motor Neurons ◽

Parasympathetic Nervous System ◽

Ganglion Cells ◽

Reflex Response ◽

Retinal Ganglion ◽

Choroidal Blood Flow

The functions of the eye are regulated by and dependent upon the autonomic nervous system. The parasympathetic nervous system controls constriction of the iris and accommodation of the lens via a pathway with preganglionic motor neurons in the Edinger-Westphal nucleus and postganglionic motor neurons in the ciliary ganglion. The parasympathetic nervous system regulates choroidal blood flow and the production of aqueous humor through a pathway with preganglionic motor neurons in the superior salivatory nucleus and postganglionic motor neurons in the pterygopalatine (sphenopalatine) ganglion. The sympathetic nervous system controls dilation of the iris and may modulate the outflow of aqueous humor from the eye. The sympathetic preganglionic motor neurons lie in the intermediolateral cell column at the first level of the thoracic cord, and the postganglionic motor neurons are found in the superior cervical ganglion. The central pathways controlling different autonomic functions in the eye are found in a variety of locations within the central nervous system. The reflex response of the iris to changes in luminance levels begins with melanopsin-containing retinal ganglion cells in the retina that project to the olivary pretectal nucleus. This nucleus then projects upon the Edinger-Westphal preganglionic motoneurons. The dark response that produces maximal pupillary dilation involves the sympathetic pathways to the iris. Pupil size is also regulated by many other factors, but the pathways to the parasympathetic and sympathetic preganglionic motoneurons that underlie this are not well understood. Lens accommodation is controlled by premotor neurons located in the supraoculomotor area. These also regulate the pupil, and control vergence angle by modulating the activity of medial rectus, and presumably lateral rectus, motoneurons. Pathways from the frontal eye fields and cerebellum help regulate their activity. Blood flow in the choroid is regulated with respect to systemic blood pressure through pathways through the nucleus of the tractus solitarius. It is also regulated with respect to luminance levels, which likely involves the suprachiasmatic nucleus, which receives inputs from melanopsin-containing retinal ganglion cells, and other areas of the hypothalamus that project upon the parasympathetic preganglionic neurons of the superior salivatory nucleus that mediate choroidal vasodilation.

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Architecture of retinal projections to the central circadian pacemaker

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1523629113 ◽

2016 ◽

Vol 113 (21) ◽

pp. 6047-6052 ◽

Cited By ~ 53

Author(s):

Diego Carlos Fernandez ◽

Yi-Ting Chang ◽

Samer Hattar ◽

Shih-Kuo Chen

Keyword(s):

Retinal Ganglion Cells ◽

Ganglion Cells ◽

Microscopic Analysis ◽

Brain Regions ◽

Retinal Ganglion ◽

Circadian Pacemaker ◽

Retinal Neurons ◽

Retinal Input ◽

Innervation Patterns ◽

Left And Right

The suprachiasmatic nucleus (SCN) receives direct retinal input from the intrinsically photosensitive retinal ganglion cells (ipRGCs) for circadian photoentrainment. Interestingly, the SCN is the only brain region that receives equal inputs from the left and right eyes. Despite morphological assessments showing that axonal fibers originating from ipRGCs cover the entire SCN, physiological evidence suggests that only vasoactive intestinal polypeptide (VIP)/gastrin-releasing peptide (GRP) cells located ventrally in the SCN receive retinal input. It is still unclear, therefore, which subpopulation of SCN neurons receives synaptic input from the retina and how the SCN receives equal inputs from both eyes. Here, using single ipRGC axonal tracing and a confocal microscopic analysis in mice, we show that ipRGCs have elaborate innervation patterns throughout the entire SCN. Unlike conventional retinal ganglion cells (RGCs) that innervate visual targets either ipsilaterally or contralaterally, a single ipRGC can bilaterally innervate the SCN. ipRGCs form synaptic contacts with major peptidergic cells of the SCN, including VIP, GRP, and arginine vasopressin (AVP) neurons, with each ipRGC innervating specific subdomains of the SCN. Furthermore, a single SCN-projecting ipRGC can send collateral inputs to many other brain regions. However, the size and complexity of the axonal arborizations in non-SCN regions are less elaborate than those in the SCN. Our results provide a better understanding of how retinal neurons connect to the central circadian pacemaker to synchronize endogenous circadian clocks with the solar day.

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Tbr2-expressing retinal ganglion cells are ipRGCs

10.1101/2020.06.17.153551 ◽

2020 ◽

Author(s):

Chai-An Mao ◽

Ching-Kang Chen ◽

Takae Kiyama ◽

Nicole Weber ◽

Christopher M. Whitaker ◽

...

Keyword(s):

Retinal Ganglion Cells ◽

Molecular Mechanisms ◽

Ganglion Cells ◽

Amacrine Cells ◽

Primary Component ◽

Retinal Ganglion ◽

Retinal Neurons ◽

T Box ◽

Retinofugal Projections ◽

A Minor

AbstractThe mammalian retina contains more than 40 retinal ganglion cell (RGC) subtypes based on their unique morphologies, functions, and molecular profiles. Among them, intrinsically photosensitive RGCs (ipRGCs) are the first specified RGC type that emerged from a common pool of retinal progenitor cells. Previous work has shown that T-box transcription factor T-brain 2 (Tbr2) is essential for the formation and maintenance of ipRGCs, and Tbr2-expressing RGCs activate Opn4 expression upon native ipRGC loss, suggesting that Tbr2+ RGCs can serve as a reservoir for ipRGCs. However, the identity of Tbr2+ RGCs has not been fully vetted, and the developmental and molecular mechanisms underlying the formation of native and reservoir ipRGCs remain unclear. Here, we showed that Tbr2-expressing retinal neurons include RGCs and GABAergic displaced amacrine cells (dACs). Using genetic sparse labeling, we demonstrated that the majority of Tbr2+ RGCs are intrinsically photosensitive and morphologically indistinguishable from known ipRGC types and have identical retinofugal projections. Additionally, we found a minor fraction of Pou4f1-expressing Tbr2+ RGCs marks a unique OFF RGC subtype. Most of the Tbr2+ RGCs can be ablated by anti-melanopsin-SAP toxin in adult retinas, supporting that Tbr2+ RGCs contain reservoir ipRGCs that express melanopsin at varying levels. When Tbr2 is deleted in adult retinas, Opn4 expression is diminished followed by the death of Tbr2-deficient cells, suggesting that Tbr2 is essential for both Opn4 expression and ipRGC survival. Finally, Tbr2 extensively occupies multiple T-elements in the Opn4 locus, indicating a direct regulatory role for Tbr2 on Opn4 transcription.Significance statementMelanopsin/Opn4-expressing intrinsically photosensitive retinal ganglion cells (ipRGCs) play fundamental roles in non-image forming vision. Previously we identified Tbr2 as the key transcription regulator for the development and maintenance of ipRGCs. To reveal the full identity of Tbr2-expressing retinal neurons and how Tbr2 acts, we generated a novel mouse line to genetically label and study Tbr2-expressing cells. Our in-depth characterizations firmly established that most Tbr2+ RGCs are indeed ipRGCs and that Tbr2 regulates Opn4 transcription, thus place Tbr2-Opn4 transcription regulatory hierarchy as the primary component in the development and maintenance of the non-image forming visual system.

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Laminin receptors in the retina: sequence analysis of the chick integrin alpha 6 subunit. Evidence for transcriptional and posttranslational regulation.

The Journal of Cell Biology ◽

10.1083/jcb.113.2.405 ◽

1991 ◽

Vol 113 (2) ◽

pp. 405-416 ◽

Cited By ~ 102

Author(s):

I de Curtis ◽

V Quaranta ◽

R N Tamura ◽

L F Reichardt

Keyword(s):

Retinal Ganglion Cells ◽

Ganglion Cells ◽

Developmental Regulation ◽

Cell Types ◽

Laminin Receptor ◽

Retinal Ganglion ◽

Retinal Neurons ◽

Laminin Receptors ◽

Chick Retina ◽

Integrin Alpha 6

The integrin alpha 6 beta 1 is a prominent laminin receptor used by many cell types. In the present work, we isolate clones and determine the primary sequence of the chick integrin alpha 6 subunit. We show that alpha 6 beta 1 is a prominent integrin expressed by cells in the developing chick retina. Between embryonic days 6 and 12, both retinal ganglion cells and other retinal neurons lose selected integrin functions, including the ability to attach and extend neurites on laminin. In retinal ganglion cells, we show that this is correlated with a dramatic decrease in alpha 6 mRNA and protein, suggesting that changes in gene expression account for the developmental regulation of the interactions of these neurons with laminin. In other retinal neurons the expression of alpha 6 mRNA and protein remains high while function is lost, suggesting that the function of the alpha 6 beta 1 heterodimer in these cells is regulated by posttranslational mechanisms.

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Pigment Epithelium-Derived Factor (PEDF) Receptors Are Involved in Survival of Retinal Neurons

International Journal of Molecular Sciences ◽

10.3390/ijms22010369 ◽

2020 ◽

Vol 22 (1) ◽

pp. 369

Author(s):

Susanne Bürger ◽

Jie Meng ◽

Annette Zwanzig ◽

Mike Beck ◽

Maik Pankonin ◽

...

Keyword(s):

Retinal Ganglion Cells ◽

Ganglion Cells ◽

Pigment Epithelium ◽

Laminin Receptor ◽

Retinal Ganglion ◽

Retinal Neurons ◽

Differential Survival ◽

Hypoxic Conditions ◽

Pigment Epithelium Derived Factor ◽

Inhibition Of Angiogenesis

The demise of retinal ganglion cells (RGCs) is characteristic of diseases of the retina such as glaucoma and diabetic or ischemic retinopathies. Pigment epithelium-derived factor (PEDF) is a multifunctional secreted protein that mediates neuroprotection and inhibition of angiogenesis in the retina. We have studied expression and regulation of two of several receptors for PEDF, patatin-like phospholipase 2 gene product/PEDF-R and laminin receptor (LR), in serum-starved RGC under normoxia and hypoxia and investigated their involvement in the survival of retinal neuronal cells. We show that PEDF-R and LR are co-expressed in RGC and R28 retinal precursor cells. Expression of both receptors was enhanced in the presence of complex secretions from retinal glial (Müller) cells and upregulated by VEGF and under hypoxic conditions. PEDF-R- and LR-knocked-down cells demonstrated a markedly attenuated expression of anti-apoptotic Bcl-2 family members (Bcl-2, Bcl-xL) and neuroprotective mediators (PEDF, VEGF, BDNF) suggesting that both PEDF-R and LR mediate pro-survival effects of PEDF on RGC. While this study does not provide evidence for a differential survival-promoting influence of either PEDF-R or LR, it nevertheless highlights the importance of both PEDF receptors for the viability of retinal neurons.

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Localization of laminin B1 mRNA in retinal ganglion cells by in situ hybridization.

The Journal of Cell Biology ◽

10.1083/jcb.110.6.2099 ◽

1990 ◽

Vol 110 (6) ◽

pp. 2099-2108 ◽

Cited By ~ 43

Author(s):

P V Sarthy ◽

M Fu

Keyword(s):

Extracellular Matrix ◽

Nervous System ◽

In Situ Hybridization ◽

Ganglion Cell ◽

Retinal Ganglion Cells ◽

Ganglion Cells ◽

Matrix Proteins ◽

Retinal Ganglion ◽

Mrna Synthesis

In the nervous system, neuronal migration and axonal growth are dependent on specific interactions with extracellular matrix proteins. During development of the vertebrate retina, ganglion cell axons extend along the internal limiting (basement) membrane and form the optic nerve. Laminin, a major component of basement membranes, is known to be present in the internal limiting membrane, and might be involved in the growth of ganglion cell axons. The identity of the cells that produce retinal laminin, however, has not been established. In the present study, we have used in situ hybridization to localize the sites of laminin B1 mRNA synthesis in the developing mouse retina. Our results show that there are at least two principal sites of laminin B1 mRNA synthesis: (a) the hyaloid vessels and the lens during the period of major axonal outgrowth, and (b) the retinal ganglion cells at later development stages. Müller (glial) cells, the major class of nonneuronal cells in the retina, do not appear to express laminin B1 mRNA either during development or in the adult retina. In Northern blots, we found a single transcript of approximately 6-kb size that encodes the laminin B1 chain in the retina. Moreover, laminin B1 mRNA level was four- to fivefold higher in the postnatal retina compared to that in the adult. Our results show that in addition to nonneuronal cells, retinal ganglion cells also synthesize laminin. The function of laminin in postnatal retinas, however, remains to be elucidated. Nevertheless, our findings raise the possibility that neurons in other parts of the nervous system might also synthesize extracellular matrix proteins.

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