Self-organized formation of polarized cortical tissues from ESCs and its active manipulation by extrinsic signals.
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.
Eiraku
Mototsugu
M
Organogenesis and Neurogenesis Group, RIKEN Center for Developmental Biology, Kobe 650-0047, Japan.
Watanabe
Kiichi
K
Matsuo-Takasaki
Mami
M
Kawada
Masako
M
Yonemura
Shigenobu
S
Matsumura
Michiru
M
Wataya
Takafumi
T
Nishiyama
Ayaka
A
Muguruma
Keiko
K
Sasai
Yoshiki
Y
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
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