Functional Assembly of Accessory Optic System Circuitry Critical for Compensatory Eye Movements

Sun, Lu; Brady, Colleen; Cahill, Hugh; Al-Khindi, Timour; Sakuta, Hiraki; Dhande, Onkar S.; Noda, Masaharu; Huberman, Andrew D.; Nathans, Jeremy; Kolodkin, Alex L.

doi:10.1016/j.neuron.2015.03.064

Cited by 86 publications

(90 citation statements)

References 48 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Combining these observations with recent evidence indicating that PlxnA2/PlxnA4 − Sema6A reverse signaling occurs in vitro [36] and regulates axon guidance and targeting during murine optic system development [37], it can be hypothesized that PlxnA2 and PlxnA4 may act as a guidance cue for dLGN axons in the vTel, at the level of the IC. In this scenario, PlxnA2/PlxnA4 could provide, for instance, a repellent signal constraining axonal growth within the IC and acting specifically on Sema6A-positive dLGN projections.…”

Section: Discussionmentioning

confidence: 56%

Semaphorin-Plexin signaling influences early ventral telencephalic development and thalamocortical axon guidance

2017

View full text Add to dashboard Cite

BackgroundSensory processing relies on projections from the thalamus to the neocortex being established during development. Information from different sensory modalities reaching the thalamus is segregated into specialized nuclei, whose neurons then send inputs to cognate cortical areas through topographically defined axonal connections.Developing thalamocortical axons (TCAs) normally approach the cortex by extending through the subpallium; here, axonal navigation is aided by distributed guidance cues and discrete cell populations, such as the corridor neurons and the internal capsule (IC) guidepost cells. In mice lacking Semaphorin-6A, axons from the dorsal lateral geniculate nucleus (dLGN) bypass the IC and extend aberrantly in the ventral subpallium. The functions normally mediated by Semaphorin-6A in this system remain unknown, but might depend on interactions with Plexin-A2 and Plexin-A4, which have been implicated in other neurodevelopmental processes.MethodsWe performed immunohistochemical and neuroanatomical analyses of thalamocortical wiring and subpallial development in Sema6a and Plxna2; Plxna4 null mutant mice and analyzed the expression of these genes in relevant structures.ResultsIn Plxna2; Plxna4 double mutants we discovered TCA pathfinding defects that mirrored those observed in Sema6a mutants, suggesting that Semaphorin-6A − Plexin-A2/Plexin-A4 signaling might mediate dLGN axon guidance at subpallial level.In order to understand where and when Semaphorin-6A, Plexin-A2 and Plexin-A4 may be required for proper subpallial TCA guidance, we then characterized their spatiotemporal expression dynamics during early TCA development. We observed that the thalamic neurons whose axons are misrouted in these mutants normally express Semaphorin-6A but not Plexin-A2 or Plexin-A4. By contrast, all three proteins are expressed in corridor cells and other structures in the developing basal ganglia.This finding could be consistent with an hypothetical action of Plexins as guidance signals through Sema6A as a receptor on dLGN axons, and/or with their indirect effect on TCA guidance due to functions in the morphogenesis of subpallial intermediate targets. In support of the latter possibility, we observed that in both Plxna2; Plxna4 and Sema6a mutants some IC guidepost cells abnormally localize in correspondence of the ventral path misrouted TCAs elongate into.ConclusionsThese findings implicate Semaphorin-6A − Plexin-A2/Plexin-A4 interactions in dLGN axon guidance and in the spatiotemporal organization of guidepost cell populations in the mammalian subpallium.Electronic supplementary materialThe online version of this article (doi:10.1186/s13064-017-0083-4) contains supplementary material, which is available to authorized users.

show abstract

Section: Discussionmentioning

confidence: 56%

Semaphorin-Plexin signaling influences early ventral telencephalic development and thalamocortical axon guidance

2017

View full text Add to dashboard Cite

show abstract

“…For example, co-expression of Ephrins and Eph-receptors in cis can alter responses to these proteins in trans [107]. Similar modulatory interactions in cis have been observed for Class 6 Semaphorins and Plexin-A proteins, thus generating combinatorial functional diversity [108–110]. Cadherins and protocadherins can also form heteromeric complexes, either within or across these two subfamilies [111, 112], which can alter function, as with a cis interaction between Pcdh19 and Cdh2, which generates a novel trans-adhesive complex [113].…”

Section: Discussionmentioning

confidence: 99%

A dual-strategy expression screen for candidate connectivity labels in the developing thalamus

et al. 2017

View full text Add to dashboard Cite

The thalamus or “inner chamber” of the brain is divided into ~30 discrete nuclei, with highly specific patterns of afferent and efferent connectivity. To identify genes that may direct these patterns of connectivity, we used two strategies. First, we used a bioinformatics pipeline to survey the predicted proteomes of nematode, fruitfly, mouse and human for extracellular proteins containing any of a list of motifs found in known guidance or connectivity molecules. Second, we performed clustering analyses on the Allen Developing Mouse Brain Atlas data to identify genes encoding surface proteins expressed with temporal profiles similar to known guidance or connectivity molecules. In both cases, we then screened the resultant genes for selective expression patterns in the developing thalamus. These approaches identified 82 candidate connectivity labels in the developing thalamus. These molecules include many members of the Ephrin, Eph-receptor, cadherin, protocadherin, semaphorin, plexin, Odz/teneurin, Neto, cerebellin, calsyntenin and Netrin-G families, as well as diverse members of the immunoglobulin (Ig) and leucine-rich receptor (LRR) superfamilies, receptor tyrosine kinases and phosphatases, a variety of growth factors and receptors, and a large number of miscellaneous membrane-associated or secreted proteins not previously implicated in axonal guidance or neuronal connectivity. The diversity of their expression patterns indicates that thalamic nuclei are highly differentiated from each other, with each one displaying a unique repertoire of these molecules, consistent with a combinatorial logic to the specification of thalamic connectivity.

show abstract

“…Evidence of a more instructional role for reverse signaling was found in a subset of On direction-selective ganglion cells (OnDSGCs). Here, Sema6A mediates axonal targeting to the accessory optic system (AOS) through an attractive response to Plexin A2 and A4 (Sun et al, 2015). Although it is clear that the capability of transmembrane Semas to signal in reverse and function as axon guidance receptors is highly conserved, it had not been previously known whether Sema reverse signaling contributes directly to midline crossing.…”

Section: Discussionmentioning

confidence: 99%

Sema-1a Reverse Signaling Promotes Midline Crossing in Response to Secreted Semaphorins

2017

View full text Add to dashboard Cite

SUMMARY Commissural axons must cross the midline to form functional midline circuits. In the invertebrate nerve cord and vertebrate spinal cord, midline crossing is mediated in part by Netrin-dependent chemoattraction. Loss of crossing, however, is incomplete in mutants for Netrin or its receptor Frazzled/DCC, suggesting the existence of additional pathways. We identified the transmembrane Semaphorin, Sema-1a, as an important regulator of midline crossing in the Drosophila CNS. We show that in response to the secreted Semaphorins Sema-2a and Sema-2b, Sema-1a functions as a receptor to promote crossing independently of Netrin. In contrast to other examples of reverse signaling where Sema1a triggers repulsion through activation of Rho in response to Plexin binding, in commissural neurons Sema-1a acts independently of Plexins to inhibit Rho to promote attraction to the midline. These findings suggest that Sema-1a reverse signaling can elicit distinct axonal responses depending on differential engagement of distinct ligands and signaling effectors.

show abstract

Functional Assembly of Accessory Optic System Circuitry Critical for Compensatory Eye Movements

Cited by 86 publications

References 48 publications

Semaphorin-Plexin signaling influences early ventral telencephalic development and thalamocortical axon guidance

Semaphorin-Plexin signaling influences early ventral telencephalic development and thalamocortical axon guidance

A dual-strategy expression screen for candidate connectivity labels in the developing thalamus

Sema-1a Reverse Signaling Promotes Midline Crossing in Response to Secreted Semaphorins

Contact Info

Product

Resources

About