Jones Bradley W, Abeysekera Matthew, Galinska Jolanta, Jolicoeur Ethel M
Molecular Neurobiology Program, Skirball Institute of Biomolecular Medicine, and Department of Pharmacology, New York University School of Medicine, New York, NY 10016, USA.
Dev Biol. 2004 Feb 15;266(2):374-87. doi: 10.1016/j.ydbio.2003.10.013.
In Drosophila, glial cell differentiation requires the expression of glial cells missing (gcm) in multiple neural cell lineages, where gcm acts as a binary switch for glial vs. neuronal fate. Thus, the primary event controlling gliogenesis in neural progenitors is the transcription of gcm. In addition, gcm is also required for the differentiation of macrophages, and is expressed in the hemocyte lineage. This dual role of gcm in glial cell and blood cell development underscores the need for the precise temporal and spatial regulation of gcm transcription. To understand how gcm transcription is regulated, we have undertaken an analysis of the cis-regulatory DNA elements of gcm using lacZ reporter activity in transgenic embryos, testing the activity of approximately 35 kilobases of DNA from the gcm locus. We have identified several distinct DNA regions that promote most of the elements of gcm expression. These include elements for general neural expression, gcm-independent and gcm-dependent glial-specific expression, as well as early and late hemocyte expression. We show that expression of an abdominal glial-specific element is dependent on the homeotic gene abdominal-A. Our results indicate that gcm transcription is controlled by a combination of general and lineage-specific elements, positive autoregulation, and neuronal repression.
在果蝇中，神经胶质细胞的分化需要多个神经细胞谱系中缺失神经胶质细胞（gcm）的表达，其中gcm作为神经胶质细胞与神经元命运的二元开关。因此，控制神经祖细胞中神经胶质细胞生成的主要事件是gcm的转录。此外，gcm也是巨噬细胞分化所必需的，并在血细胞谱系中表达。gcm在神经胶质细胞和血细胞发育中的双重作用突出了对gcm转录进行精确的时间和空间调控的必要性。为了了解gcm转录是如何被调控的，我们利用转基因胚胎中的lacZ报告基因活性对gcm的顺式调控DNA元件进行了分析，测试了来自gcm基因座约35千碱基的DNA的活性。我们鉴定出了几个不同的DNA区域，它们促进了gcm表达的大部分元件。这些区域包括一般神经表达元件、不依赖gcm和依赖gcm的神经胶质细胞特异性表达元件，以及早期和晚期血细胞表达元件。我们表明，腹部神经胶质细胞特异性元件的表达依赖于同源异型基因腹部-A。我们的结果表明，gcm转录受一般元件和谱系特异性元件、正向自调控以及神经元抑制的共同控制。
