Lupo Giuseppe, Bertacchi Michele, Carucci Nicoletta, Augusti-Tocco Gabriella, Biagioni Stefano, Cremisi Federico
Department of Biology and Biotechnology "C. Darwin", Sapienza University of Rome, Piazzale Aldo Moro 5, 00185, Rome, Italy,
Cell Mol Life Sci. 2014 Aug;71(15):2917-30. doi: 10.1007/s00018-014-1596-1. Epub 2014 Mar 19.
Embryonic stem cells (ESCs) have been used extensively as in vitro models of neural development and disease, with special efforts towards their conversion into forebrain progenitors and neurons. The forebrain is the most complex brain region, giving rise to several fundamental structures, such as the cerebral cortex, the hypothalamus, and the retina. Due to the multiplicity of signaling pathways playing different roles at distinct times of embryonic development, the specification and patterning of forebrain has been difficult to study in vivo. Research performed on ESCs in vitro has provided a large body of evidence to complement work in model organisms, but these studies have often been focused more on cell type production than on cell fate regulation. In this review, we systematically reassess the current literature in the field of forebrain development in mouse and human ESCs with a focus on the molecular mechanisms of early cell fate decisions, taking into consideration the specific culture conditions, exogenous and endogenous molecular cues as described in the original studies. The resulting model of early forebrain induction and patterning provides a useful framework for further studies aimed at reconstructing forebrain development in vitro for basic research or therapy.
胚胎干细胞（ESCs）已被广泛用作神经发育和疾病的体外模型，并特别致力于将其转化为前脑祖细胞和神经元。前脑是最复杂的脑区，产生几种基本结构，如大脑皮层、下丘脑和视网膜。由于多种信号通路在胚胎发育的不同时间发挥不同作用，前脑的特化和模式形成在体内很难研究。在体外对胚胎干细胞进行的研究提供了大量证据来补充模式生物的研究工作，但这些研究通常更多地关注细胞类型的产生，而不是细胞命运的调控。在这篇综述中，我们系统地重新评估了小鼠和人类胚胎干细胞前脑发育领域的现有文献，重点关注早期细胞命运决定的分子机制，同时考虑到原始研究中描述的特定培养条件、外源性和内源性分子信号。由此产生的早期前脑诱导和模式形成模型为进一步研究提供了一个有用的框架，这些研究旨在为基础研究或治疗在体外重建前脑发育。
