Sherman Jonathan H, Karpinski Beverly A, Fralish Matthew S, Cappuzzo Justin M, Dhindsa Devinder S, Thal Arielle G, Moody Sally A, LaMantia Anthony S, Maynard Thomas M
Department of Neurological Surgery, George Washington University Hospital, Washington, District of Columbia.
Institute for Neuroscience, George Washington University, Washington, District of Columbia.
Genesis. 2017 Jun;55(6). doi: 10.1002/dvg.23031. Epub 2017 Apr 3.
Many molecular factors required for later stages of neuronal differentiation have been identified; however, much less is known about the early events that regulate the initial establishment of the neuroectoderm. We have used an in vitro embryonic stem cell (ESC) differentiation model to investigate early events of neuronal differentiation and to define the role of mouse Foxd4, an ortholog of a forkhead-family transcription factor central to Xenopus neural plate/neuroectodermal precursor development. We found that Foxd4 is a necessary regulator of the transition from pluripotent ESC to neuroectodermal stem cell, and its expression is necessary for neuronal differentiation. Mouse Foxd4 expression is not only limited to the neural plate but it is also expressed and apparently functions to regulate neurogenesis in the olfactory placode. These in vitro results suggest that mouse Foxd4 has a similar function to its Xenopus ortholog; this was confirmed by successfully substituting murine Foxd4 for its amphibian counterpart in overexpression experiments. Thus, Foxd4 appears to regulate the initial steps in establishing neuroectodermal precursors during initial development of the nervous system.
许多神经元分化后期所需的分子因子已被确定；然而，对于调节神经外胚层初始形成的早期事件，我们了解得还很少。我们利用体外胚胎干细胞（ESC）分化模型来研究神经元分化的早期事件，并确定小鼠Foxd4的作用，Foxd4是叉头家族转录因子的直系同源物，对非洲爪蟾神经板/神经外胚层前体发育至关重要。我们发现，Foxd4是多能ESC向神经外胚层干细胞转变的必要调节因子，其表达对于神经元分化是必需的。小鼠Foxd4的表达不仅局限于神经板，它在嗅基板中也有表达，并且显然在调节神经发生中发挥作用。这些体外实验结果表明，小鼠Foxd4与其非洲爪蟾直系同源物具有相似的功能；在过表达实验中成功地用小鼠Foxd4替代其两栖类对应物证实了这一点。因此，Foxd4似乎在神经系统初始发育过程中调节神经外胚层前体建立的初始步骤。
