Self-Organized Formation of Polarized Cortical Tissues from ESCs and Its Active Manipulation by Extrinsic Signals

Mototsugu Eiraku, Kiichi Watanabe, Mami Matsuo-Takasaki, Masako Kawada, Shigenobu Yonemura, Michiru Matsumura, Takafumi Wataya, Ayaka Nishiyama, Keiko Muguruma, Yoshiki Sasai

Research output: Contribution to journalArticlepeer-review

934 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)519-532
Number of pages14
JournalCell Stem Cell
Volume3
Issue number5
DOIs
Publication statusPublished - 06-11-2008
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Genetics
  • Cell Biology

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