CyclinD2-mediated regulation of neurogenic output from the retinal ciliary margin is perturbed in albinism
In albinism, aberrations in the ipsi-/contralateral retinal ganglion cell (RGC) ratio compromise the functional integrity of the binocular circuit. Here, we focus on the mouse ciliary margin zone (CMZ), a neurogenic niche at the embryonic peripheral retina, to investigate developmental processes reg...
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Published in | Neuron (Cambridge, Mass.) Vol. 111; no. 1; pp. 49 - 64.e5 |
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Main Authors | , , , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
United States
Elsevier Inc
04.01.2023
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Subjects | |
Online Access | Get full text |
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Summary: | In albinism, aberrations in the ipsi-/contralateral retinal ganglion cell (RGC) ratio compromise the functional integrity of the binocular circuit. Here, we focus on the mouse ciliary margin zone (CMZ), a neurogenic niche at the embryonic peripheral retina, to investigate developmental processes regulating RGC neurogenesis and identity acquisition. We found that the mouse ventral CMZ generates predominantly ipsilaterally projecting RGCs, but this output is altered in the albino visual system because of CyclinD2 downregulation and disturbed timing of the cell cycle. Consequently, albino as well as CyclinD2-deficient pigmented mice exhibit diminished ipsilateral retinogeniculate projection and poor depth perception. In albino mice, pharmacological stimulation of calcium channels, known to upregulate CyclinD2 in other cell types, augmented CyclinD2-dependent neurogenesis of ipsilateral RGCs and improved stereopsis. Together, these results implicate CMZ neurogenesis and its regulators as critical for the formation and function of the mammalian binocular circuit.
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•The mouse CMZ is functionally important for the development of binocular vision•In albinism, CyclinD2 downregulation in the CMZ prolongs G1/S phase transition•CyclinD2 deficiency compromises ipsilateral RGC neurogenesis and depth perception•Modulation of calcium channels in the albino CMZ restores binocular vision
This article is an in-depth investigation of molecular alterations underlying chiasmatic misrouting in the albino binocular circuit. During development, in a specialized retinal niche—the ciliary margin—fewer cells express the cell-cycle regulator CyclinD2. Consequently, the cell cycle is elongated, resulting in fewer ipsilaterally projecting RGCs and perturbed binocular vision. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Authors contributed equally AUTHOR CONTRIBUTIONS Conceptualization: NS, SK, CAM; Methodology: NS, SK, CAM; Investigation: NS, RB, MAL, ML, ROL, JP; Resources: AP, CMT, MER; Writing - Review & Editing: NS, EH, SWMJ, CAM; Formal analysis: NS, RB, ML; Supervision: NS, CAM; Software: RB; Validation: NS, ML; Visualization: NS, CAM; Project administration: CAM; Funding acquisition: CAM |
ISSN: | 0896-6273 1097-4199 1097-4199 |
DOI: | 10.1016/j.neuron.2022.10.025 |