Ipsilateral and Contralateral Retinal Ganglion Cells Express Distinct Genes during Decussation at the Optic Chiasm

Wang, Qing; Marcucci, Florencia; Cerullo, Isadora; Mason, Carol A.

doi:10.1523/eneuro.0169-16.2016

Cited by 46 publications

(78 citation statements)

References 83 publications

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“…Several lines of evidence point to Cyclin D2 as a key regulator of cell cycle progression and neurogenesis (Glickstein et al, ; Komada, Iguchi, Takeda, Ishibashi, & Sato, ; Petros et al, ; Tsunekawa et al, ; Tsunekawa & Osumi, ). Gene profiling revealed that Cyclin D2 is differentially expressed in the mouse retina, with more cells expressing Cyclin D2 in the ventral than in the dorsal CMZ (Wang et al, ). In addition, in the absence of Cyclin D2, a reduced number of i‐ and cRGCs are found in VT retina and the ipsilateral projection is reduced, indicating that a subset of i‐ and cRGC progenitors reside in the ventral CMZ (Marcucci et al, ).…”

Section: Resultsmentioning

confidence: 99%

“…We analyzed the fraction of cells that exit the cell cycle by injecting EdU at E13 and determining the coincidence of EdU and Ki67 in the CMZ at E14.5, comparing Cyclin D2 −/− to Cyclin D2 +/+ littermates. Cyclin D2 is enriched in ventral CMZ and expressed at low levels in dorsal CMZ, and is absent from the neural retina, including the sectors named as peripheral neural retina in Figure a,b (Marcucci et al, ; Wang et al, ). Hence, we compared cell cycle exit in ventral and dorsal CMZ and in ventral and dorsal peripheral retina.…”

Section: Resultsmentioning

confidence: 99%

“…Several lines of evidence point to Cyclin Ds as key regulators of cell cycle dynamics and cell fate determination (Tsunekawa et al, ), but the exact mechanisms are unclear (Tsunekawa & Osumi, ). Our recent work reveals that Cyclin D2 is enriched in the ventral ciliary margin zone (CMZ) (Q. Wang et al, ), and that in the absence of Cyclin D2, neurogenesis of i‐ and cRGC subtypes is diminished and the ipsi projection is decreased (Marcucci et al, ). Moreover, live imaging showed that during embryogenesis, cells translocate from the CMZ to the neural retina, implicating the embryonic mammalian CMZ as a source of RGCs (Marcucci et al, ).…”

Section: Introductionmentioning

confidence: 99%

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Distinct timing of neurogenesis of ipsilateral and contralateral retinal ganglion cells

Marcucci

Soares

Mason

2018

J of Comparative Neurology

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In higher vertebrates, the circuit formed by retinal ganglion cells (RGCs) projecting ipsilaterally (iRGCs) or contralaterally (cRGCs) to the brain permits binocular vision and depth perception. iRGCs and cRGCs differ in their position within the retina and in expression of transcription, guidance and activity-related factors. To parse whether these two populations also differ in the timing of their genesis, a feature of distinct neural subtypes and associated projections, we used newer birthdating methods and cell subtype specific markers to determine birthdate and cell cycle exit more precisely than previously. In the ventrotemporal (VT) retina, i- and cRGCs intermingle and neurogenesis in this zone lags behind RGC production in the rest of the retina where only cRGCs are positioned. In addition, within the VT retina, i- and cRGC populations are born at distinct times: neurogenesis of iRGCs surges at E13, and cRGCs arise as early as E14, not later in embryogenesis as reported. Moreover, in the ventral ciliary margin zone (CMZ), which contains progenitors that give rise to some iRGCs in ventral neural retina (Marcucci et al., 2016), cell cycle exit is slower than in other retinal regions in which progenitors give rise only to cRGCs. Further, when the cell cycle regulator Cyclin D2 is missing, cell cycle length in the CMZ is further reduced, mirroring the reduction of both i- and cRGCs in the Cyclin D2 mutant. These results strengthen the view that differential regulation of cell cycle dynamics at the progenitor level is associated with specific RGC fates and laterality of axonal projection.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Distinct timing of neurogenesis of ipsilateral and contralateral retinal ganglion cells

Marcucci

Soares

Mason

2018

J of Comparative Neurology

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“…Hes5 is expressed in Ki67 + progenitor cells in the neuroblastic layer but not in the ciliary marginal zone (CMZ) which is a source of RGCs (Marcucci et al, 2016; Wang et al, 2016). Notch1 is also highly expressed in the neuroblastic layer and moderately expressed in the RGC layer.…”

Section: Resultsmentioning

confidence: 99%

“…How is proliferation and differentiation of ipsilateral RGCs which are situated in VT retina, regulated? Most recently, we have identified Cyclin D2 as a regulator of cell cycle progression and exit in VT retina during the production of Zic2 + RGCs (Marcucci et al, 2016; Wang et al, 2016). As overexpression of Hes5 in VT retina has no effect on RGC differentiation, contralateral and ipsilateral RGC differentiation may be mediated by distinct molecules and/or downstream signals of Hes5.…”

Section: Discussionmentioning

confidence: 99%

SoxC Transcription Factors Promote Contralateral Retinal Ganglion Cell Differentiation and Axon Guidance in the Mouse Visual System

Kuwajima

Soares

Sitko

et al. 2017

Neuron

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Summary Transcription factors control cell identity by regulating diverse developmental steps such as differentiation and axon guidance. The mammalian binocular visual circuit is comprised of projections of retinal ganglion cells (RGCs) to ipsilateral and contralateral targets in the brain. A transcriptional code for ipsilateral RGC identity has been identified, but less is known about the transcriptional regulation of contralateral RGC development. Here we demonstrate that SoxC genes (Sox4, 11, and 12) act on the progenitor-to-postmitotic transition to implement contralateral, but not ipsilateral, RGC differentiation, by binding to Hes5 and thus repressing Notch signaling. When SoxC genes are deleted in postmitotic RGCs, contralateral RGC axons grow poorly on chiasm cells in vitro, project ipsilaterally at the chiasm midline in vivo, and Plexin-A1 and Nr-CAM expression in RGCs is downregulated. These data implicate SoxC transcription factors in the regulation of contralateral RGC differentiation and axon guidance.

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Multiomic Analysis of Neurons with Divergent Projection Patterns Identifies Novel Regulators of Axon Pathfinding

et al. 2022

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Axon pathfinding is a key step in neural circuits formation. However, the transcriptional mechanisms regulating its progression remain poorly understood. The binary decision of crossing or avoiding the midline taken by some neuronal axons during development represents a robust model to investigate the mechanisms that control the selection of axonal trajectories. Here, to identify novel regulators of axon guidance, this work compares the transcriptome and chromatin occupancy profiles of two neuronal subpopulations, ipsilateral (iRGC) and contralateral retinal ganglion cells (cRGC), with similar functions but divergent axon trajectories. These analyses retrieved a number of genes encoding for proteins not previously implicated in axon pathfinding. In vivo functional experiments confirm the implication of some of these candidates in axonal navigation. Among the candidate genes, 𝜸-synuclein is identified as essential for inducing midline crossing. Footprint and luciferase assays demonstrate that this small-sized protein is regulated by the transcription factor (TF) Pou4f1 in cRGCs. It is also shown that Lhx2/9 are specifically expressed in iRGCs and control a program that partially overlaps with that regulated by Zic2, previously described as essential for iRGC specification. Overall, the analyses identify dozens of new molecules potentially involved in axon guidance and reveal the regulatory logic behind the selection of axonal trajectories.

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Ipsilateral and Contralateral Retinal Ganglion Cells Express Distinct Genes during Decussation at the Optic Chiasm

Abstract: Visual Abstract

Cited by 46 publications

References 83 publications

Distinct timing of neurogenesis of ipsilateral and contralateral retinal ganglion cells

Distinct timing of neurogenesis of ipsilateral and contralateral retinal ganglion cells

SoxC Transcription Factors Promote Contralateral Retinal Ganglion Cell Differentiation and Axon Guidance in the Mouse Visual System

Multiomic Analysis of Neurons with Divergent Projection Patterns Identifies Novel Regulators of Axon Pathfinding

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