TY - JOUR
T1 - Self-formation of concentric zones of telencephalic and ocular tissues and directional retinal ganglion cell axons
AU - Liu, Wei
AU - Shrestha, Rupendra
AU - Lowe, Albert
AU - Zhang, Xusheng
AU - Spaeth, Ludovic
N1 - Publisher Copyright:
© 2023, eLife Sciences Publications Ltd. All rights reserved.
PY - 2023
Y1 - 2023
N2 - The telencephalon and eye in mammals are originated from adjacent fields at the anterior neural plate. Morphogenesis of these fields generates telencephalon, optic-stalk, optic-disc, and neuroretina along an axis. How these telencephalic and ocular tissues are specified coordinately to ensure directional retinal ganglion cell (RGC) axon growth is unclear. Here, we report the self-formation of human telencephalon-eye organoids comprising concentric zones of telencephalic, optic-stalk, optic-disc, and neuroretinal tissues along the center-periphery axis. Initially-differentiated RGCs grew axons towards and then along a path defined by adjacent PAX2+ optic-disc cells. Single-cell RNA sequencing identified expression signatures of two PAX2+ cell populations that mimic optic-disc and optic-stalk, respectively, mechanisms of early RGC differentiation and axon growth, and RGC-specific cell-surface protein CNTN2, leading to one-step purification of electrophysiologically-excitable RGCs. Our findings provide insight into the coordinated specification of early telencephalic and ocular tissues in humans and establish resources for studying RGC-related diseases such as glaucoma.
AB - The telencephalon and eye in mammals are originated from adjacent fields at the anterior neural plate. Morphogenesis of these fields generates telencephalon, optic-stalk, optic-disc, and neuroretina along an axis. How these telencephalic and ocular tissues are specified coordinately to ensure directional retinal ganglion cell (RGC) axon growth is unclear. Here, we report the self-formation of human telencephalon-eye organoids comprising concentric zones of telencephalic, optic-stalk, optic-disc, and neuroretinal tissues along the center-periphery axis. Initially-differentiated RGCs grew axons towards and then along a path defined by adjacent PAX2+ optic-disc cells. Single-cell RNA sequencing identified expression signatures of two PAX2+ cell populations that mimic optic-disc and optic-stalk, respectively, mechanisms of early RGC differentiation and axon growth, and RGC-specific cell-surface protein CNTN2, leading to one-step purification of electrophysiologically-excitable RGCs. Our findings provide insight into the coordinated specification of early telencephalic and ocular tissues in humans and establish resources for studying RGC-related diseases such as glaucoma.
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U2 - 10.7554/eLife.87306.1
DO - 10.7554/eLife.87306.1
M3 - Article
C2 - 37665325
AN - SCOPUS:85165343694
SN - 2050-084X
VL - 12
JO - eLife
JF - eLife
ER -