Department of Pediatrics, Alberta Children's Hospital Research Institute, University of Calgary, Calgary, Alberta, Canada.
Department of Pathology & Laboratory Medicine, Southern Alberta Cancer Research Institute, University of Calgary, Calgary, Alberta, Canada.
Curr Top Dev Biol. 2014;110:75-127. doi: 10.1016/B978-0-12-405943-6.00002-6.
Proneural genes encode evolutionarily conserved basic-helix-loop-helix transcription factors. In Drosophila, proneural genes are required and sufficient to confer a neural identity onto naïve ectodermal cells, inducing delamination and subsequent neuronal differentiation. In vertebrates, proneural genes are expressed in cells that already have a neural identity, but they are still required and sufficient to initiate neurogenesis. In all organisms, proneural genes control neurogenesis by regulating Notch-mediated lateral inhibition and initiating the expression of downstream differentiation genes. The general mode of proneural gene function has thus been elucidated. However, the regulatory mechanisms that spatially and temporally control proneural gene function are only beginning to be deciphered. Understanding how proneural gene function is regulated is essential, as aberrant proneural gene expression has recently been linked to a variety of human diseases-ranging from cancer to neuropsychiatric illnesses and diabetes. Recent insights into proneural gene function in development and disease are highlighted herein.
神经前基因编码进化上保守的碱性螺旋-环-螺旋转录因子。在果蝇中，神经前基因是将原始外胚层细胞赋予神经特性所必需和充分的，诱导细胞脱离并随后进行神经元分化。在脊椎动物中，神经前基因在已经具有神经特性的细胞中表达，但它们仍然是启动神经发生所必需和充分的。在所有生物体中，神经前基因通过调节 Notch 介导的侧向抑制和启动下游分化基因的表达来控制神经发生。因此，已经阐明了神经前基因的一般功能模式。然而，空间和时间上控制神经前基因功能的调节机制才刚刚开始被破译。理解神经前基因功能是如何被调控的至关重要，因为最近已经发现异常的神经前基因表达与多种人类疾病有关，从癌症到神经精神疾病和糖尿病。本文重点介绍了神经前基因在发育和疾病中的功能的最新见解。
