Department of Morphological Neural Science, Graduate School of Medical Sciences, Kumamoto University, 1-1-1, Honjo, Chuo-ku, Kumamoto, 860-8556, Japan.
Department of Brain Morphogenesis, Institute of Molecular Embryology and Genetics (IMEG), Kumamoto University, 2-2-1, Honjo, Chuo-ku, Kumamoto, 860-0811, Japan.
Biochem Biophys Res Commun. 2020 Mar 26;524(1):117-122. doi: 10.1016/j.bbrc.2020.01.070. Epub 2020 Jan 21.
The telencephalon is one of the most-elaborated tissues. A broad variety of cell types is produced by spatiotemporally regulated mechanisms and is involved, in different combinations, in subregional formation. The dorsal half of the telencephalon, the pallium or cerebral cortex, is subdivided along the dorsal-ventral (D-V) axis into the medial, dorsal, lateral, and ventral pallium (MP, DP, LP and VP, respectively). An in vitro differentiation system has been achieved using mouse embryonic stem cells, and major telencephalic neurons can be obtained in this way; however, in using the in vitro differentiation system, many telencephalic neuron subtypes remain undifferentiated, although some of them are related to neuronal diseases. In the current study, we found that inhibiting the TGFbeta signal was efficient for neural induction. A continuous arrangement of Emx1+/Pax6-, Emx1+/Pax6+, and Emx1-/Pax6+ cells was achieved in Foxg1+ neuroepithelia, corresponding approximately to cortical progenitors derived from MP, DP/LP, and VP, respectively. A small portion of Dbx1+ cells resided in the VP fraction. These findings suggested that the D-V axis of the pallium was recapitulated in the in vitro-derived pallium.
端脑是最发达的组织之一。通过时空调节机制产生了广泛多样的细胞类型，并以不同的组合方式参与亚区形成。端脑的背侧部，即大脑皮层，沿背腹（D-V）轴分为内侧、背侧、外侧和腹侧大脑皮层（MP、DP、LP 和 VP）。已经使用小鼠胚胎干细胞实现了体外分化系统，并且可以通过这种方式获得主要的大脑皮层神经元；然而，在使用体外分化系统时，许多大脑皮层神经元亚型仍然未分化，尽管其中一些与神经元疾病有关。在本研究中，我们发现抑制 TGFbeta 信号对于神经诱导是有效的。在 Foxg1+神经上皮中，实现了 Emx1+/Pax6-、Emx1+/Pax6+和 Emx1-/Pax6+细胞的连续排列，分别对应于来自 MP、DP/LP 和 VP 的皮质祖细胞。一小部分 Dbx1+细胞存在于 VP 部分。这些发现表明，大脑皮层的 D-V 轴在体外衍生的大脑皮层中得到了再现。
