TY - JOUR
KW - Adults
KW - Bright field microscopy
KW - In Situ Hybridization
KW - organoids
KW - Photoreceptors
KW - RNA hybridization
KW - Retina
KW - Transfection
AU - Sarah E. Hadyniak
AU - Joanna F. D. Hagen
AU - Kiara C. Eldred
AU - Boris Brenerman
AU - Katarzyna A. Hussey
AU - Rajiv C. McCoy
AU - Michael E. G. Sauria
AU - James A. Kuchenbecker
AU - Thomas Reh
AU - Ian Glass
AU - Maureen Neitz
AU - Jay Neitz
AU - James Taylor
AU - Robert J. Johnston Jr
AB - Trichromacy is unique to primates among placental mammals, enabled by blue (short/S), green (medium/M), and red (long/L) cones. In humans, great apes, and Old World monkeys, cones make a poorly understood choice between M and L cone subtype fates. To determine mechanisms specifying M and L cones, we developed an approach to visualize expression of the highly similar M- and L-opsin mRNAs. M-opsin was observed before L-opsin expression during early human eye development, suggesting that M cones are generated before L cones. In adult human tissue, the early-developing central retina contained a mix of M and L cones compared to the late-developing peripheral region, which contained a high proportion of L cones. Retinoic acid (RA)-synthesizing enzymes are highly expressed early in retinal development. High RA signaling early was sufficient to promote M cone fate and suppress L cone fate in retinal organoids. Across a human population sample, natural variation in the ratios of M and L cone subtypes was associated with a noncoding polymorphism in the NR2F2 gene, a mediator of RA signaling. Our data suggest that RA promotes M cone fate early in development to generate the pattern of M and L cones across the human retina.
BT - PLOS Biology
DA - Jan 11, 2024
DO - 10.1371/journal.pbio.3002464
IS - 1
LA - en
N2 - Trichromacy is unique to primates among placental mammals, enabled by blue (short/S), green (medium/M), and red (long/L) cones. In humans, great apes, and Old World monkeys, cones make a poorly understood choice between M and L cone subtype fates. To determine mechanisms specifying M and L cones, we developed an approach to visualize expression of the highly similar M- and L-opsin mRNAs. M-opsin was observed before L-opsin expression during early human eye development, suggesting that M cones are generated before L cones. In adult human tissue, the early-developing central retina contained a mix of M and L cones compared to the late-developing peripheral region, which contained a high proportion of L cones. Retinoic acid (RA)-synthesizing enzymes are highly expressed early in retinal development. High RA signaling early was sufficient to promote M cone fate and suppress L cone fate in retinal organoids. Across a human population sample, natural variation in the ratios of M and L cone subtypes was associated with a noncoding polymorphism in the NR2F2 gene, a mediator of RA signaling. Our data suggest that RA promotes M cone fate early in development to generate the pattern of M and L cones across the human retina.
PY - 0
EP - e3002464
T2 - PLOS Biology
TI - Retinoic acid signaling regulates spatiotemporal specification of human green and red cones
UR - https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.3002464
VL - 22
Y2 - 2024-08-13
SN - 1545-7885
ER -