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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Bibliographic Details
Authors: Slavi, Nefeli, Balasubramanian, Revathi, Lee, Melissa Ann, Liapin, Michael, Oaks-Leaf, Rachel, Peregrin, John, Potenski, Anna, Troy, Carol Marie, Ross, Margaret Elizabeth, Herrera, Eloisa, Kosmidis, Stylianos, John, Simon William Maxwell, Mason, Carol Ann
Format: article
Status:Published version
Publication Date:2023
Country:España
Institution:Consejo Superior de Investigaciones Científicas (CSIC)
Repository:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/309056
Online Access:http://hdl.handle.net/10261/309056
Access Level:Open access
Keyword:Retinal ganglion cells
Neurogenesis
Ipsilateral projection
CyclinD2
Ciliary margin
Albinism
RPE
Single-cell RNA seq
Binocular vision
Description
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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