Hardwick Laura J A, Philpott Anna
Wellcome-MRC Cambridge Stem Cell Institute, University of Cambridge, Cambridge, CB2 1QR, UK.
Department of Oncology, University of Cambridge, Cambridge, CB2 0XZ, UK.
Wellcome Open Res. 2018 Sep 26;3:125. doi: 10.12688/wellcomeopenres.14842.1. eCollection 2018.
The proneural basic-helix-loop-helix (bHLH) transcription factor Ascl1 is a master regulator of neurogenesis in both central and peripheral nervous systems and is a central driver of neuronal reprogramming . Over the last three decades, assaying primary neuron formation in embryos in response to transcription factor overexpression has contributed to our understanding of the roles and regulation of proneural proteins like Ascl1, with homologues from different species usually exhibiting similar functional effects. Here we demonstrate that the mouse Ascl1 protein is twice as active as the protein in inducing neural-β-tubulin expression in embryos, despite there being little difference in protein accumulation or ability to undergo phosphorylation, two properties known to influence Ascl1 function. This superior activity of the mouse compared to the protein is dependent on the presence of the non-conserved N terminal region of the protein, and indicates species-specific regulation that may necessitate care when interpreting results in cross-species experiments.
神经前体碱性螺旋-环-螺旋（bHLH）转录因子Ascl1是中枢和外周神经系统神经发生的主要调节因子，也是神经元重编程的核心驱动因素。在过去三十年中，通过检测胚胎中因转录因子过表达而产生的原代神经元形成，有助于我们理解像Ascl1这样的神经前体蛋白的作用和调控，不同物种的同源物通常表现出相似的功能效应。在这里，我们证明，尽管在蛋白质积累或磷酸化能力方面几乎没有差异（这两个特性已知会影响Ascl1的功能），但小鼠Ascl1蛋白在诱导胚胎中神经β-微管蛋白表达方面的活性是[未提及的物种]蛋白的两倍。与[未提及的物种]蛋白相比，小鼠的这种优越活性取决于该蛋白非保守N端区域的存在，这表明存在物种特异性调控，在解释跨物种实验结果时可能需要谨慎。
