PAX6 is essential for neural retina (NR) and forebrain development but howPAX6 instructsNRversus forebrain specification remains unknown. We found that the paired-lessPAX6,PAX6D, is expressed inNRcells during human eye development and along human embryonic stem cell (hESC) specification to retinal cells.hESCs deficient forPAX6D failed to enterNRspecification. Induced expression ofPAX6D but notPAX6A in aPAX6-null background restored theNRspecification capacity. ChIP-Seq, confirmed by functional assays, revealed a set of retinal genes and non-retinal neural genes that are potential targets ofPAX6D, includingWNT8B. Inhibition ofWNTs or knocking down ofWNT8B restored theNRspecification capacity of neuroepithelia withPAX6D knockout, whereas activation ofWNTs blockedNRspecification even whenPAX6D was induced. Thus,PAX6D specifies neuroepithelia toNRcells via the regulation ofWNT8B.
基金：
NIH-NINDSUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of Neurological Disorders & Stroke (NINDS) [NS096282, NS086604]; NIH-NIMHUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of Mental Health (NIMH) [MH100031]; NICHDUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD) [U54 HD090256]; Ministry of Education of SingaporeMinistry of Education, Singapore [MOE2018T2-2-103]; Bleser Family Foundation; Busta Foundation; UW Foundation; [1S100OD018202-01]
生物