Retinal axon pathfinding in the optic chiasm: Divergence of crossed and uncrossed fibers

doi:10.1016/0896-6273(90)90307-2

Neuron

Volume 5, Issue 2, August 1990, Pages 173-186

https://doi.org/10.1016/0896-6273(90)90307-2 Get rights and content

Abstract

In the developing mammalian visual system, retinal fibers grow through the optic chiasm, where one population crosses to the opposite side of the brain and the other does not. Evidence from labeling growing retinal axons with the carbocyanine dye Dil in mouse embryos indicates that the two subpopulations diverge at a zone along the midline of the optic chiasm. At the border of this zone, crossed fibers grow directly across, whereas uncrossed fibers turn back, developing highly complex terminations with bifurcating and wide-ranging growth cones. When one eye is removed at early stages, uncrossed fibers from the remaining eye stall at the chiasm midline. These results suggest that crossed and uncrossed retinal fibers respond differently to cues along the midline of the chiasm and that the uncrossed fibers from one eye grow along crossed fibers from the other eye, both guidance mechanisms contributing to the establishment of the bilateral pattern of visual projections in mammalian brain.

References (56)

M.J. Bastiani et al.
Expression of fasciclin I and II glycoproteins on subsets of axon pathways during neuronal development in the grasshopper
Cell
(1987)
S.M. Bunt et al.
Prenatal development of the optic projection in albino and hooded rats
Dev. Brain Res.
(1983)
J. Dodd et al.
Spatial regulation of glycoprotein expression on subsets of embryonic spinal neurons
Neuron
(1988)
J.S. Eisen et al.
The growth cones of identified motoneurons in embyonic zebrafish select appropriate pathways in the absence of specific cellular interactions
Neuron
(1989)
J.K. Ivins et al.
Growth cone-growth cone interactions in cultures of rat sympathetic neurons
Dev. Biol.
(1989)
P.C. Letourneau
Cell-to-substratum adhesion and guidance of axonal elongation
Dev. Biol.
(1975)
C.A. Mason
How do growth cones grow?
Trends Neurosci.
(1985)
P.H. Patterson
On the importance of being inhibited, or saying no to growth cones
Neuron
(1988)
R.N. Pittman
Release of plasminogen activator and a calcium-dependent metalloprotease from cultured sympathetic and sensory neurons
Dev. Biol.
(1985)
P.H. Taghert et al.
Guidance of pioneer growth cones: filopodial contacts and coupling revealed with antibody to Lucifer Yellow
Dev. Biol.
(1982)

M.J. Bastiani et al.

Neuronal growth cones: specific interactions mediated by filopodial insertion and induction of coated vesicles

M.J. Bastiani et al.

Guidance of neuronal growth cones in the grasshopper embryo. I. Recognition of a specific axonal pathway by the pCC neuron

J. Neurosci.

(1986)

C.M. Bate

Pioneer neurons in an insect embryo

Nature

(1976)

D. Bentley et al.

Pioneer axons lose directed growth after selective killing of guidepost cells

Nature

(1983)

D. Bentley et al.

Disoriented pathfinding by pioneer neurone growth cones deprived of filopodia by cytochalasin treatment

Nature

(1986)

J. Berlot et al.

Guidance of peripheral pioneer neurons in the grasshopper: adhesive hierarchy of epithelial and neuronal surfaces

Science

(1984)

F. Bonhoeffer et al.

In vitro experiments demonstrating an ante ro-posterior gradient on the tectum

EMBO J.

(1980)

F. Bonhoeffer et al.

Position-dependent properties of retinal axons and their growth cones

Nature

(1985)

P. Bovolenta et al.

Guidance of commissural growth cones at the floor plate in embryonic rat spinal cord

Development

(1990)

R. Bovolenta et al.

Growth cone morphology varies with position in the developing mouse visual pathway from retina to first targets

J. Neurosci.

(1987)

D.W. Burmeister et al.

Micropruning: the mechanism of turning of Aplysia growth cones at substrate borders in vitro

J. Neurosci.

(1988)

M. Caudy et al.

Pioneer growth cone morphologies reveal proximal increases in substrate affinity within leg segments of grasshopper embryos

J. Neurosci.

(1986)

R.J. Colello et al.

The early development of retinal ganglion cells with uncrossed axons in the mouse: retinal position and axonal course

Development

(1990)

J. Dodd et al.

Axon guidance and the patterning of neuronal projections in vertebrates

Science

(1988)

J.S. Edwards et al.

Cercal sensory development following laser microlesions of embryonic apical cells in Acheta domesticus

J. Neurosci.

(1981)

P. Godement et al.

Absence de projections rétiniennes ipsilatérales après destruction très précoce in utero d'un oeil chez la souris

CR Acad. Sci. Paris, Série III

(1981)

P. Godement et al.

Fate of uncrossed retinal projections following early or late prenatal monocular enucleation in the mouse

J. Comp. Neurol.

(1987)

P. Godement et al.

A study in developing visual systems with a new method of staining neurones and their processes in fixed tissue

Development

(1987)

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But, how would I be able to see uncrossed retinal fibers? Years before, a paper in rats had shown that initially (in rats, around E16-17) a small part of the temporal ventral retina sends only uncrossed fibers to the brain (Bunt et al., 1983, their Figures 10–14; see also, Fig. 1 in Godement et al., 1990). Crossed fibers originated from the rest of the retina, that is, at the exclusion of this area.
The main focus of research for which Friedrich Bonhoeffer’s work is known in the Neuroscience community was pioneer experiments on how axonal projections could organize into “maps”, what mechanisms are involved in axon guidance and involve gradients of guiding molecules, and isolation of the first such molecules, e.g. RAGS (ephrin A5) and RGM (repulsive guidance molecule). Other papers have described in detail these contributions as well as Friedrich Bonhoeffer’s personality. In the mid-eighties, I made a 2-year stay in his lab and initiated a line of research on development of binocular connections in Mammals, particularly the guidance of retinal fibers to one or the other side of the brain. In this paper I recall these circumstances as they pertain to Neuroscience as it stood at the time, and explain as best as I can how his lab was a conducive setting for the discoveries made there and how Friedrich Bonhoeffer acted for me as a scientist and a tutor.
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Our earlier studies have shown that the axon growth inhibitory molecule Nogo affects axon routing at the optic chiasm likely through a differential regulation of Nogo receptor on the optic axons. Using isoform specific antibodies, we further showed that Nogo-A was predominantly expressed by retinal ganglion cells and their axons, while Nogo-B was highly localized on the radial glia at the midline of the chiasm, suggesting a role of Nogo-B in regulating turning of uncrossed axons. To further investigate the roles of Nogo-A in axon divergence, we analyzed the routing of axons in the chiasm of Nogo-A knockout mice during the growth of axons across the midline. At E13 to E16, there was no significant difference in the contralateral projection (P = 0.6943 for E13; P = 0.9867 for E14; P = 0.4121 for E15 and P = 0.3402 for E16). The results also showed the absence of Nogo-A did not cause any obvious change to the ipsilateral projection at the optic chiasm, both for the early generated uncrossed axons at E13 and E14 and the late cohorts at E15-E16, when compared with the wild-type mice (P = 0.4788 for E13; P = 0.188 for E14; P = 0.3152 for E15 and P = 0.432 for E16). These findings support that Nogo-A is not the major isoform to guide the axon divergence in the mouse optic chiasm.
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Our previous studies showed interaction of Nogo at the midline with its receptor (NgR) on optic axons plays a role in axon divergence at the mouse optic chiasm. Since NgR lacks a cytoplasmic domain, it needs transmembrane receptor partners for signal transduction. In this study, we examined whether the co-receptors of NgR, low-affinity neurotrophic receptor (p75^NTR) and Lingo-1, are localized on axons in the mouse optic pathway. In the retina, p75^NTR and Lingo-1 were observed on neuroepithelial cells at E13 and later on the retinal ganglion cells at E14 and E15. At the optic disc, p75^NTR was observed on the retinal axons, whereas Lingo-1 was found on glial processes surrounding the axon fascicles. Both p75^NTR and Lingo-1 were found on axons in the optic stalk, optic chiasm and optic tract. Furthermore, a transient expression of Lingo-1 was observed on the SSEA-1 positive chiasmatic neurons at E13, but not at later developmental stages. The presence of p75^NTR and Lingo-1 on optic axons provides further supports to the contribution of Nogo/NgR signaling in axon divergence at the mouse optic chiasm.
Dopamine signaling regulates the projection patterns in the mouse chiasm
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Citation Excerpt :
In all retinal growth cones examined, OA1 was identified on retinal growth cones from both the dorsal nasal (DN; crossing axons) and VT (uncrossing axons) (Fig. 2G and H). From E13-E15, many RGC previously crossed the OC and arrived at the OT, and these cells subsequently underwent axon sorting (Godement et al., 1990). OA1 staining in the frontal sections of the ventral diencephalon was identified in axons in the OS, OC and OT (Fig. 2I–K).
Ocular albinism (OA) is characterized by inadequate L-3, 4-dihydroxyphenylalanine (L-DOPA) and dopamine (DA) in the eyes. This study investigated DA-related signaling pathways in mouse chiasm projection patterns and the potential role of ocular albinism type 1 (OA1) and dopamine 1A (D1A) receptors in the optic pathway. In embryonic day (E) E13-E15 retina, most L-DOPA and OA1-positive cells were distributed among Müller glial cells on E13 and retinal ganglion cells (RGC) on E14. In the ventral diencephalon, OA1 and L-DOPA were strongly expressed on the optic chiasm (OC) and optic tract (OT), respectively, but weak on the optic stalk (OS). At E13-E15, DA and D1A staining was predominately expressed in radially arranged cells with a neuronal expression pattern. In the ventral diencephalon, DA and D1A were strongly expressed on the OC, OT and OS. Furthermore, L-DOPA significantly inhibited retinal axon outgrowth in both the dorsal nasal (DN) and ventral temporal (VT) groups. DA inhibited retinal axon outgrowth, which was abolished by the D1A antagonist SCH23390. Brain slice cultures indicated that L-DOPA inhibited axons that crossed at the OC of E13 embryos, which was not abolished by DA. L-DOPA also inhibited axons that crossed at the OC of albino mice. Albino mice exhibited reduced ipsilateral retinal projections compared with C57 pigmented mice. No significant difference was identified in the uncrossed projections of albino mice following L-DOPA and DA expression. Furthermore, transcription factor Zic family member 2 (Zic2) upregulated OA1 mRNA expression. Our findings provide critical insights into DA-related signaling in retinal development.
Localization of protein kinase C isoforms in the optic pathway of mouse embryos and their role in axon routing at the optic chiasm
2014, Brain Research
Citation Excerpt :
In mouse embryos, RGC axons navigate through the optic stalk and the chiasm at ventral midline of the diencephalon. Within this structure, axons from peripheral parts of the ventrotemporal retina (or temporal crescent) are deflected from the midline and grow into the optic tract on the same side, whereas axons from the rest (or nasal) of the retina decussate to the contralateral optic tract (Colello and Guillery, 1990; Godement et al., 1987, 1990) (Fig. 1), establishing a bilaterally projecting pathway that is essential for binocular vision in mammals. Previous findings in the mouse have shown that this axon routing pattern is controlled by inhibitory molecules expressed on some early generated neurons and radial glial cells in the optic chiasm.
Protein kinase C (PKC) plays a key role in many receptor-mediated signaling pathways that regulate cell growth and development. However, its roles in guiding axon growth and guidance in developing neural pathways are largely unknown. To investigate possible functions of PKC in the growth and guidance of axons in the optic chiasm, we first determined the localization of major PKC isoforms in the retinofugal pathway of mouse embryos, at the stage when axons navigate through the midline. Results showed that PKC was expressed in isoform specific patterns in the pathway. PKC-α immunoreactivity was detected in the chiasm and the optic tract. PKC-βΙΙ was strong in the optic stalk but was attenuated on axons in the diencephalon. Immunostaining for PKC-ε showed a colocalization in the chiasmatic neurons that express a surface antigen stage specific embryonic antigen-1 (SSEA-1). These chiasmatic neurons straddled the midline of the optic chiasm, and have been shown in earlier studies a role in regulation of axon growth and guidance. Expression levels of PKC-βΙ, -δ and -γ were barely detectable in the pathway. Blocking of PKC signaling with Ro-32-0432, an inhibitor specific for PKC-α and -β at nanomolar concentration, produced a dramatic reduction of ipsilateral axons from both nasal retina and temporal crescent. We conclude from these studies that PKC-α and -βΙΙ are the predominant forms in the developing optic pathway, whereas PKC-ε is the major form in the chiasmatic neurons. Furthermore, PKC-α and -βΙΙ are likely involved in signaling pathways triggered by inhibitory molecules at the midline that guide optic axons to the uncrossed pathway.
Development of the retina and optic pathway
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Citation Excerpt :
Additionally, in most non-primate mammals, many cells in the temporal retina project contralaterally rather than ipsilaterally, complicating any simple morphogenetic account based upon retinotopic fiber order. Birth-dating studies showed that the uncrossed component from the temporal retina was generated earlier than was the crossed temporal component (Dräger, 1985; Reese & Colello, 1992), while tract-tracing studies during development confirmed that the uncrossed component reached the brain prior to the crossed component (Baker & Reese, 1993; Godement, Salaun, & Mason, 1990; Sretavan, 1990). Other studies in carnivores confirmed that ganglion cell classes with partial decussation patterns were generated prior to, and gave rise to axons arriving earlier than, those with more complete decussations (Reese & Baker, 1990; Reese, Guillery, & Mallarino, 1992; Reese, Guillery, Marzi, & Tassinari, 1991; Reese, Thompson, & Peduzzi, 1994; Walsh, Polley, Hickey, & Guillery, 1983).
Our understanding of the development of the retina and visual pathways has seen enormous advances during the past 25 years. New imaging technologies, coupled with advances in molecular biology, have permitted a fuller appreciation of the histotypical events associated with proliferation, fate determination, migration, differentiation, pathway navigation, target innervation, synaptogenesis and cell death, and in many instances, in understanding the genetic, molecular, cellular and activity-dependent mechanisms underlying those developmental changes. The present review considers those advances associated with the lineal relationships between retinal nerve cells, the production of retinal nerve cell diversity, the migration, patterning and differentiation of different types of retinal nerve cells, the determinants of the decussation pattern at the optic chiasm, the formation of the retinotopic map, and the establishment of ocular domains within the thalamus.

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Neuron

ArticleRetinal axon pathfinding in the optic chiasm: Divergence of crossed and uncrossed fibers

Abstract

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J. Neurosci.

Pioneer neurons in an insect embryo

Nature

Pioneer axons lose directed growth after selective killing of guidepost cells

Nature

Disoriented pathfinding by pioneer neurone growth cones deprived of filopodia by cytochalasin treatment

Nature

Guidance of peripheral pioneer neurons in the grasshopper: adhesive hierarchy of epithelial and neuronal surfaces

Science

In vitro experiments demonstrating an ante ro-posterior gradient on the tectum

EMBO J.

Position-dependent properties of retinal axons and their growth cones

Nature

Guidance of commissural growth cones at the floor plate in embryonic rat spinal cord

Development

Growth cone morphology varies with position in the developing mouse visual pathway from retina to first targets

J. Neurosci.

Micropruning: the mechanism of turning of Aplysia growth cones at substrate borders in vitro

J. Neurosci.

Pioneer growth cone morphologies reveal proximal increases in substrate affinity within leg segments of grasshopper embryos

J. Neurosci.

The early development of retinal ganglion cells with uncrossed axons in the mouse: retinal position and axonal course

Development

Axon guidance and the patterning of neuronal projections in vertebrates

Science

Cercal sensory development following laser microlesions of embryonic apical cells in Acheta domesticus

J. Neurosci.

Absence de projections rétiniennes ipsilatérales après destruction très précoce in utero d'un oeil chez la souris

CR Acad. Sci. Paris, Série III

Fate of uncrossed retinal projections following early or late prenatal monocular enucleation in the mouse

J. Comp. Neurol.

A study in developing visual systems with a new method of staining neurones and their processes in fixed tissue

Development

Article
Retinal axon pathfinding in the optic chiasm: Divergence of crossed and uncrossed fibers