Organization of Axons in Their Tracts

Sitko, Austen A.; Mason, Carol A.

doi:10.1016/b978-0-12-801393-9.00013-x

“…While topographic organization of RGC axons in the optic nerve and tract has been documented previously, there is disagreement over the extent and details of organization among retinofugal axons, in part due to variable and non‐standard planes of section and diverse labeling schemes across studies. Few reports studied the mouse (Chan & Chung, ; Plas et al, ), with many more favoring the visual systems of the rat, ferret, cat, or amphibians (reviewed in Sitko & Mason, ). Furthermore, none of the studies directly compared topographic and eye‐specific order in the nerve and tract.…”

Section: Resultsmentioning

confidence: 99%

“…Three organizational modes have been identified in axon tracts in several systems and species: topography, typography, and chronotopy (reviewed in Sitko & Mason, ). Topography, based on the spatial arrangement of neurons, is the most commonly identified organizational feature in neural circuits and axon tracts.…”

Section: Introductionmentioning

confidence: 99%

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Eye‐specific segregation and differential fasciculation of developing retinal ganglion cell axons in the mouse visual pathway

Sitko

¹

,

Kuwajima

²

,

Mason

³

2018

J of Comparative Neurology

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Prior to forming and refining synaptic connections, axons of projection neurons navigate long distances to their targets. While much is known about guidance cues for axon navigation through intermediate choice points, whether and how axons are organized within tracts is less clear. Here we analyze the organization of retinal ganglion cell (RGC) axons in the developing mouse retinogeniculate pathway. RGC axons are organized by both eye-specificity and topography in the optic nerve and tract: ipsilateral RGC axons are segregated from contralateral axons and are offset laterally in the tract relative to contralateral axon topographic position. To identify potential cell-autonomous factors contributing to the segregation of ipsilateral and contralateral RGC axons in the visual pathway, we assessed their fasciculation behavior in a retinal explant assay. Ipsilateral RGC neurites self-fasciculate more than contralateral neurites in vitro and maintain this difference in the presence of extrinsic chiasm cues. To further probe the role of axon self-association in circuit formation in vivo, we examined RGC axon organization and fasciculation in an EphB1−/− mutant, in which a subset of ipsilateral RGC axons aberrantly crosses the midline but targets the ipsilateral zone in the dorsal lateral geniculate nucleus on the opposite side. Aberrantly crossing axons retain their association with ipsilateral axons in the contralateral tract, indicating that cohort-specific axon affinity is maintained independently of guidance signals present at the midline. Our results provide a comprehensive assessment of RGC axon organization in the retinogeniculate pathway and suggest that axon self-association contributes to pre-target axon organization.

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“…Our axonal growth simulations are only for pioneer axons. Many other axons may reach their remote target through fasciculation with a pioneer axon than by pure pioneering themselves [47]. However, these follower axons could still use the same guidance mechanism as pioneers to make decisions for (de-)fasciculation, so avoiding additional encoding as to when to fasciculate with which other axon.…”

Section: Discussionmentioning

confidence: 99%

Constructive Connectomics: how neuronal axons get from here to there using gene-expression maps derived from their family trees

Kerstjens

¹

,

Michel

²

,

Douglas

³

2022

Preprint

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During brain development, billions of axons must navigate over multiple spatial scales to reach specific neuronal targets, and so build the processing circuits that generate the intelligent behavior of animals. However, the limited information capacity of the zygotic genome puts a strong constraint on how, and which, axonal routes can be encoded. We propose and validate a mechanism of development that can provide an efficient encoding of this global wiring task. The key principle, confirmed through simulation, is that basic constraints on mitoses of neural stem cells—that mitotic daughters have similar gene expression to their parent and do not stray far from one another—induce a global hierarchical map of nested regions, each marked by the expression profile of its common progenitor population. Thus, a traversal of the lineal hierarchy generates a systematic sequence of expression profiles that traces a staged route, which growth cones can follow to their remote targets. We have analyzed gene expression data of developing and adult mouse brains published by the Allen Institute for Brain Science, and found them consistent with our simulations: gene expression indeed partitions the brain into a global spatial hierarchy of nested contiguous regions that is stable at least from embryonic day 11.5 to postnatal day 56. We use this experimental data to demonstrate that our axonal guidance algorithm is able to robustly extend arbors over long distances to specific targets, and that these connections result in a qualitatively plausible connectome. We conclude that, paradoxically, cell division may be the key to uniting the neurons of the brain.

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“…Our axonal growth simulations are only for pioneer axons. Many other axons may reach their remote target through fasciculation with a pioneer axon than by pure pioneering themselves [ 67 ]. However, these follower axons could still use the same guidance mechanism as pioneers to make decisions for (de-)fasciculation, so avoiding additional encoding as to when to fasciculate with which other axon.…”

Section: Discussionmentioning

confidence: 99%

Constructive connectomics: How neuronal axons get from here to there using gene-expression maps derived from their family trees

Kerstjens

¹

,

Michel

²

,

Douglas

³

2022

View full text Add to dashboard Cite

During brain development, billions of axons must navigate over multiple spatial scales to reach specific neuronal targets, and so build the processing circuits that generate the intelligent behavior of animals. However, the limited information capacity of the zygotic genome puts a strong constraint on how, and which, axonal routes can be encoded. We propose and validate a mechanism of development that can provide an efficient encoding of this global wiring task. The key principle, confirmed through simulation, is that basic constraints on mitoses of neural stem cells—that mitotic daughters have similar gene expression to their parent and do not stray far from one another—induce a global hierarchical map of nested regions, each marked by the expression profile of its common progenitor population. Thus, a traversal of the lineal hierarchy generates a systematic sequence of expression profiles that traces a staged route, which growth cones can follow to their remote targets. We have analyzed gene expression data of developing and adult mouse brains published by the Allen Institute for Brain Science, and found them consistent with our simulations: gene expression indeed partitions the brain into a global spatial hierarchy of nested contiguous regions that is stable at least from embryonic day 11.5 to postnatal day 56. We use this experimental data to demonstrate that our axonal guidance algorithm is able to robustly extend arbors over long distances to specific targets, and that these connections result in a qualitatively plausible connectome. We conclude that, paradoxically, cell division may be the key to uniting the neurons of the brain.

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Organization of Axons in Their Tracts

Cited by 6 publications

References 159 publications

Eye‐specific segregation and differential fasciculation of developing retinal ganglion cell axons in the mouse visual pathway

Eye‐specific segregation and differential fasciculation of developing retinal ganglion cell axons in the mouse visual pathway

Constructive Connectomics: how neuronal axons get from here to there using gene-expression maps derived from their family trees

Constructive connectomics: How neuronal axons get from here to there using gene-expression maps derived from their family trees

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