The Dorsoventral Patterning of Human Forebrain Follows an Activation/Transformation Model
The Dorsoventral Patterning of Human Forebrain Follows an Activation/Transformation Model
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人类前脑的背腹模式遵循激活/转化模型
DOI：
10.1093/cercor/bhw152
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发表时间：
2017-05-01
期刊：
影响因子：
3.7
通讯作者：
Zhang, Xiaoqing
中科院分区：
文献类型：
--
作者：
Chi, Liankai;Fan, Beibei;Zhang, Xiaoqing
&NA;中枢神经系统的前后模式遵循激活/转化模型，该模型提出，在神经诱导阶段，预期的端脑命运将被默认激活，而这种前命运可以根据尾化形态发生素在后面进行转化。尽管外在信号和内在转录因子都与脊椎动物端脑的背腹侧 (DV) 规范有关，但 DV 模式模型仍然难以捉摸。考虑到人类的进化特征和神经诱导过程中基因调控网络的独特性，这一点在人类中尤其如此。在这里，我们提出了一个模型，即人类前脑 DV 模式也遵循激活/转换范式。人类神经外胚层 (NE) 将自动激活前脑背侧命运，并且这种默认的前背侧命运不依赖于 Wnts 激活或 Pax6 表达。即使在声刺猬 (Shh) 处理下，Pax6 在人类 NE 中的强制表达也会阻碍其腹侧化，这表明腹侧命运受到背侧基因的抑制。 Nkx2.1（前脑腹侧祖细胞的关键基因）的遗传操作表明，Nkx2.1对于Shh驱动的腹侧化既不是必要的也不是充分的。因此，我们提出Shh抑制人类NE的背侧基因，并随后以抑制释放方式将原始激活的背侧命运转变为腹侧。
&NA; The anteroposterior patterning of the central nervous system follows an activation/transformation model, which proposes that a prospective telencephalic fate will be activated by default during the neural induction stage, while this anterior fate could be transformed posteriorly according to caudalization morphogens. Although both extrinsic signals and intrinsic transcription factors have been implicated in dorsoventral (DV) specification of vertebrate telencephalon, the DV patterning model remains elusive. This is especially true in human considering its evolutionary trait and uniqueness of gene regulatory networks during neural induction. Here, we point to a model that human forebrain DV patterning also follows an activation/transformation paradigm. Human neuroectoderm (NE) will activate a forebrain dorsal fate automatically and this default anterior dorsal fate does not depend on Wnts activation or Pax6 expression. Forced expression of Pax6 in human NE hinders its ventralization even under sonic hedgehog (Shh) treatment, suggesting that the ventral fate is repressed by dorsal genes. Genetic manipulation of Nkx2.1, a key gene for forebrain ventral progenitors, shows that Nkx2.1 is neither necessary nor sufficient for Shh‐driven ventralization. We thus propose that Shh represses dorsal genes of human NE and subsequently transforms the primitively activated dorsal fate ventrally in a repression release manner.