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PAX6D instructs neural retinal specification from human embryonic stem cell-derived neuroectoderm.
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, Su-Chun.
Affiliation
  • Tao Y; Waisman Center, University of Wisconsin-Madison, Madison, WI, USA.
  • Cao J; Waisman Center, University of Wisconsin-Madison, Madison, WI, USA.
  • Li M; Department of Rehabilitation of Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
  • Hoffmann B; Waisman Center, University of Wisconsin-Madison, Madison, WI, USA.
  • Xu K; Waisman Center, University of Wisconsin-Madison, Madison, WI, USA.
  • Chen J; Department of Rehabilitation of Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
  • Lu X; Wuhan No. 1 Hospital, Wuhan, China.
  • Guo F; Neurological Department of Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
  • Li X; Waisman Center, University of Wisconsin-Madison, Madison, WI, USA.
  • Phillips MJ; Waisman Center, University of Wisconsin-Madison, Madison, WI, USA.
  • Gamm DM; McPherson Eye Research Institute, University of Wisconsin-Madison, Madison, WI, USA.
  • Chen H; Waisman Center, University of Wisconsin-Madison, Madison, WI, USA.
  • Zhang SC; McPherson Eye Research Institute, University of Wisconsin-Madison, Madison, WI, USA.
EMBO Rep ; 21(9): e50000, 2020 09 03.
Article in En | MEDLINE | ID: mdl-32700445
ABSTRACT
PAX6 is essential for neural retina (NR) and forebrain development but how PAX6 instructs NR versus forebrain specification remains unknown. We found that the paired-less PAX6, PAX6D, is expressed in NR cells during human eye development and along human embryonic stem cell (hESC) specification to retinal cells. hESCs deficient for PAX6D failed to enter NR specification. Induced expression of PAX6D but not PAX6A in a PAX6-null background restored the NR specification capacity. ChIP-Seq, confirmed by functional assays, revealed a set of retinal genes and non-retinal neural genes that are potential targets of PAX6D, including WNT8B. Inhibition of WNTs or knocking down of WNT8B restored the NR specification capacity of neuroepithelia with PAX6D knockout, whereas activation of WNTs blocked NR specification even when PAX6D was induced. Thus, PAX6D specifies neuroepithelia to NR cells via the regulation of WNT8B.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Human Embryonic Stem Cells Limits: Humans Language: En Journal: EMBO Rep Journal subject: BIOLOGIA MOLECULAR Year: 2020 Type: Article Affiliation country: United States
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Human Embryonic Stem Cells Limits: Humans Language: En Journal: EMBO Rep Journal subject: BIOLOGIA MOLECULAR Year: 2020 Type: Article Affiliation country: United States