Premium
PAX 6D instructs neural retinal specification from human embryonic stem cell‐derived neuroectoderm
Author(s) -
Tao Yunlong,
Cao Jingyuan,
Li Mingxing,
Hoffmann Brianna,
Xu Ke,
Chen Jing,
Lu Xin,
Guo Fangliang,
Li Xiang,
Phillips M Joseph,
Gamm David M,
Chen Hong,
Zhang SuChun
Publication year - 2020
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.15252/embr.202050000
Subject(s) - library science , china , research center , political science , history , computer science , archaeology , law
PAX 6 is essential for neural retina ( NR ) and forebrain development but how PAX 6 instructs NR versus forebrain specification remains unknown. We found that the paired‐less PAX 6, PAX 6D, is expressed in NR cells during human eye development and along human embryonic stem cell ( hESC ) specification to retinal cells. hESC s deficient for PAX 6D failed to enter NR specification. Induced expression of PAX 6D but not PAX 6A in a PAX 6‐null background restored the NR specification capacity. Ch IP ‐Seq, confirmed by functional assays, revealed a set of retinal genes and non‐retinal neural genes that are potential targets of PAX 6D, including WNT 8B. Inhibition of WNT s or knocking down of WNT 8B restored the NR specification capacity of neuroepithelia with PAX 6D knockout, whereas activation of WNT s blocked NR specification even when PAX 6D was induced. Thus, PAX 6D specifies neuroepithelia to NR cells via the regulation of WNT 8B.