Biomaterial Database

PAX6D instructs neural retinal specification from human embryonic stem cell-derived neuroectoderm. 2020

Yunlong Tao, and Jingyuan Cao, and Mingxing Li, and Brianna Hoffmann, and Ke Xu, and Jing Chen, and Xin Lu, and Fangliang Guo, and Xiang Li, and M Joseph Phillips, and David M Gamm, and Hong Chen, and Su-Chun Zhang

Waisman Center, University of Wisconsin-Madison, Madison, WI, USA.

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.

UI	MeSH Term	Description	Entries
D012160	Retina	The ten-layered nervous tissue membrane of the eye. It is continuous with the OPTIC NERVE and receives images of external objects and transmits visual impulses to the brain. Its outer surface is in contact with the CHOROID and the inner surface with the VITREOUS BODY. The outer-most layer is pigmented, whereas the inner nine layers are transparent.	Ora Serrata
D002454	Cell Differentiation	Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs.	Differentiation, Cell,Cell Differentiations,Differentiations, Cell
D005136	Eye Proteins	PROTEINS derived from TISSUES of the EYE.	Proteins, Eye
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000066449	Human Embryonic Stem Cells	A type of PLURIPOTENT STEM CELLS derived from early stage human embryos, up to and including the BLASTOCYST stage.	hESC,Cells, Human Embryonic Stem,Human Embryonic Stem Cell,Stem Cells, Human Embryonic,hESCs
D051153	Wnt Proteins	Wnt proteins are a large family of secreted glycoproteins that play essential roles in EMBRYONIC AND FETAL DEVELOPMENT, and tissue maintenance. They bind to FRIZZLED RECEPTORS and act as PARACRINE PROTEIN FACTORS to initiate a variety of SIGNAL TRANSDUCTION PATHWAYS. The canonical Wnt signaling pathway stabilizes the transcriptional coactivator BETA CATENIN.	Wingless Type Protein,Wnt Factor,Wnt Protein,Wingless Type Proteins,Wnt Factors,Factor, Wnt,Protein, Wingless Type,Protein, Wnt,Type Protein, Wingless
D054258	Neural Plate	The region in the dorsal ECTODERM of a chordate embryo that gives rise to the future CENTRAL NERVOUS SYSTEM. Tissue in the neural plate is called the neuroectoderm, often used as a synonym of neural plate.	Neuroectoderm,Neural Plates,Neuroectoderms,Plate, Neural,Plates, Neural
D018398	Homeodomain Proteins	Proteins encoded by homeobox genes (GENES, HOMEOBOX) that exhibit structural similarity to certain prokaryotic and eukaryotic DNA-binding proteins. Homeodomain proteins are involved in the control of gene expression during morphogenesis and development (GENE EXPRESSION REGULATION, DEVELOPMENTAL).	Homeo Domain Protein,Homeobox Protein,Homeobox Proteins,Homeodomain Protein,Homeoprotein,Homeoproteins,Homeotic Protein,Homeo Domain Proteins,Homeotic Proteins,Domain Protein, Homeo,Protein, Homeo Domain,Protein, Homeobox,Protein, Homeodomain,Protein, Homeotic,Proteins, Homeo Domain,Proteins, Homeobox,Proteins, Homeodomain,Proteins, Homeotic