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

Organogenesis and Neurogenesis Group, RIKEN Center for Developmental Biology, Kobe 650-0047, Japan.
Cell stem cell (Impact Factor: 22.27). 12/2008; 3(5):519-32. DOI: 10.1016/j.stem.2008.09.002
Source: PubMed


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.

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    • "Human PSC-derived cortical progenitors start to generate neurons after a much longer period of about 4 weeks, instead of 6-8 days in the mouse. Similarly, the generation of distinct types of cortical neurons is also much protracted, requiring about 1 week in the mouse (Gaspard et al., 2008) but several months starting from human ESCs (Fig. 2C) (Eiraku et al., 2008; Espuny-Camacho et al., 2013; Gaspard et al., 2008; Kadoshima et al., 2013; Shi et al., 2012). Another distinctive feature proposed to link the development and evolution of human corticogenesis is the diversity of progenitors (Fig. 2A,B). "
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    Development 09/2015; 142(18):3138-3150. DOI:10.1242/dev.120568 · 6.46 Impact Factor
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    • "Collectively, these results demonstrate that the onset of UL neuron generation is controlled by the termination of DL competence, which is propagated through post-mitotic DL neurons (Toma et al., 2014). Interestingly, this signal appears to act qualitatively rather than quantitatively in vivo, where only a few postmitotic DL neurons are required to induce UL neurogenesis (Toma et al., 2014), in contrast to the requirements in vitro (Shen et al., 2006; Eiraku et al., 2008; Gaspard et al., 2008; Kadoshima et al., 2013). These observations raise the possibility that this feedback signaling may be propagated by short-range signaling through cell–cell interactions. "
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