title: Emergence of dorsal-ventral polarity in ESC-derived retinal tissue.
abstract: We previously demonstrated that mouse embryonic stem cell (mESC)-derived retinal epithelium self-forms an optic cup-like structure. In the developing retina, the dorsal and ventral sides differ in terms of local gene expression and morphological features. This aspect has not yet been shown in vitro Here, we demonstrate that mESC-derived retinal tissue spontaneously acquires polarity reminiscent of the dorsal-ventral (D-V) patterning of the embryonic retina. Tbx5 and Vax2 were expressed in a mutually exclusive manner, as seen in vivo Three-dimensional morphometric analysis showed that the in vitro-formed optic cup often contains cleft structures resembling the embryonic optic fissure. To elucidate the mechanisms underlying the spontaneous D-V polarization of mESC-derived retina, we examined the effects of patterning factors, and found that endogenous BMP signaling plays a predominant role in the dorsal specification. Further analysis revealed that canonical Wnt signaling, which was spontaneously activated at the proximal region, acts upstream of BMP signaling for dorsal specification. These observations suggest that D-V polarity could be established within the self-formed retinal neuroepithelium by intrinsic mechanisms involving the spatiotemporal regulation of canonical Wnt and BMP signals.
authors.affiliation: Laboratory for Organogenesis and Neurogenesis, RIKEN Center for Developmental Biology, 2-2-3, Minatojima-Minamimachi, Chuo, Kobe 650-0047, Japan.|Laboratory for in vitro Histogenesis, RIKEN Center for Developmental Biology, 2-2-3, Minatojima-Minamimachi, Chuo, Kobe 650-0047, Japan.
authors.forename: Yuiko
authors.initials: Y
authors.lastname: Hasegawa
authors.affiliation: Laboratory for Organogenesis and Neurogenesis, RIKEN Center for Developmental Biology, 2-2-3, Minatojima-Minamimachi, Chuo, Kobe 650-0047, Japan.|Laboratory for in vitro Histogenesis, RIKEN Center for Developmental Biology, 2-2-3, Minatojima-Minamimachi, Chuo, Kobe 650-0047, Japan.
authors.forename: Nozomu
authors.initials: N
authors.lastname: Takata
authors.affiliation: Laboratory for Organogenesis and Neurogenesis, RIKEN Center for Developmental Biology, 2-2-3, Minatojima-Minamimachi, Chuo, Kobe 650-0047, Japan.|Laboratory for in vitro Histogenesis, RIKEN Center for Developmental Biology, 2-2-3, Minatojima-Minamimachi, Chuo, Kobe 650-0047, Japan.
authors.forename: Satoru
authors.initials: S
authors.lastname: Okuda
authors.affiliation: Laboratory for Organogenesis and Neurogenesis, RIKEN Center for Developmental Biology, 2-2-3, Minatojima-Minamimachi, Chuo, Kobe 650-0047, Japan.|Laboratory for in vitro Histogenesis, RIKEN Center for Developmental Biology, 2-2-3, Minatojima-Minamimachi, Chuo, Kobe 650-0047, Japan.
authors.forename: Masako
authors.initials: M
authors.lastname: Kawada
authors.affiliation: Laboratory for Organogenesis and Neurogenesis, RIKEN Center for Developmental Biology, 2-2-3, Minatojima-Minamimachi, Chuo, Kobe 650-0047, Japan eiraku@cdb.riken.jp.|Laboratory for in vitro Histogenesis, RIKEN Center for Developmental Biology, 2-2-3, Minatojima-Minamimachi, Chuo, Kobe 650-0047, Japan.
authors.forename: Mototsugu
authors.identifier: 0000-0002-9433-9085
authors.initials: M
authors.lastname: Eiraku
authors.affiliation: Laboratory for Organogenesis and Neurogenesis, RIKEN Center for Developmental Biology, 2-2-3, Minatojima-Minamimachi, Chuo, Kobe 650-0047, Japan.
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Sasai
mesh_terms: D000818:Animals; D019521:Body Patterning / Q000502:physiology*; D016764:Cell Polarity / Q000502:physiology*; D002478:Cells, Cultured; D004622:Embryo, Mammalian; D053595:Embryonic Stem Cells / Q000166:cytology / Q000502:physiology*; D018507:Gene Expression Regulation, Developmental; D055785:Gene Knockdown Techniques; D051379:Mice; D009924:Organ Culture Techniques; D038081:Organogenesis / Q000502:physiology*; D012160:Retina / Q000166:cytology / Q000196:embryology*; D015398:Signal Transduction / Q000235:genetics
keywords: Morphogenesis; Organoid culture; Pattern formation; Retinal development