title: Self-organized formation of polarized cortical tissues from ESCs and its active manipulation by extrinsic signals.
abstract: Here, we demonstrate self-organized formation of apico-basally polarized cortical tissues from ESCs using an efficient three-dimensional aggregation culture (SFEBq culture). The generated cortical neurons are functional, transplantable, and capable of forming proper long-range connections in vivo and in vitro. The regional identity of the generated pallial tissues can be selectively controlled (into olfactory bulb, rostral and caudal cortices, hem, and choroid plexus) by secreted patterning factors such as Fgf, Wnt, and BMP. In addition, the in vivo-mimicking birth order of distinct cortical neurons permits the selective generation of particular layer-specific neurons by timed induction of cell-cycle exit. Importantly, cortical tissues generated from mouse and human ESCs form a self-organized structure that includes four distinct zones (ventricular, early and late cortical-plate, and Cajal-Retzius cell zones) along the apico-basal direction. Thus, spatial and temporal aspects of early corticogenesis are recapitulated and can be manipulated in this ESC culture.
authors.affiliation: Organogenesis and Neurogenesis Group, RIKEN Center for Developmental Biology, Kobe 650-0047, Japan.
authors.forename: Mototsugu
authors.initials: M
authors.lastname: Eiraku
authors.forename: Kiichi
authors.initials: K
authors.lastname: Watanabe
authors.forename: Mami
authors.initials: M
authors.lastname: Matsuo-Takasaki
authors.forename: Masako
authors.initials: M
authors.lastname: Kawada
authors.forename: Shigenobu
authors.initials: S
authors.lastname: Yonemura
authors.forename: Michiru
authors.initials: M
authors.lastname: Matsumura
authors.forename: Takafumi
authors.initials: T
authors.lastname: Wataya
authors.forename: Ayaka
authors.initials: A
authors.lastname: Nishiyama
authors.forename: Keiko
authors.initials: K
authors.lastname: Muguruma
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Sasai
mesh_terms: D000818:Animals; D000943:Antigens, Differentiation / Q000378:metabolism*; D019521:Body Patterning / Q000502:physiology*; D055415:Bone Morphogenetic Protein 4 / Q000378:metabolism; D002453:Cell Cycle; D002454:Cell Differentiation; D002540:Cerebral Cortex / Q000166:cytology* / Q000254:growth & development / Q000378:metabolism; D053595:Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism* / Q000637:transplantation; D051524:Fibroblast Growth Factor 8 / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D006706:Homeostasis; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D009474:Neurons / Q000166:cytology / Q000378:metabolism* / Q000637:transplantation; D015398:Signal Transduction; D046509:Tissue Culture Techniques; D051153:Wnt Proteins / Q000378:metabolism; D060508:Wnt3 Protein
chemical_list: D000943:Antigens, Differentiation; C525809:BMP4 protein, human; D055415:Bone Morphogenetic Protein 4; C496457:Fgf8 protein, mouse; D051153:Wnt Proteins; D060508:Wnt3 Protein; D051524:Fibroblast Growth Factor 8