Furman D P, Bukharina T A
Institute of Cytology and Genetics, Siberian Branch, Russian Academy of Sciences, Novosibirsk, Russia.
J Stem Cells. 2012;7(1):19-41.
Formation of specialized spatial structures comprising various cell types is most important in the ontogenesis of multicellular organisms. An example is the D. melanogaster bristle organs. Bristles (micro- and macrochaetes) are external sensory organs, elements of the peripheral nervous system, playing the role of mechanoreceptors. Their comparatively simple organization comprising only four specialized cells and a common origin of these cells make macrochaetes a convenient model for studying cell differentiation. The four cells forming bristle organ result from two successive divisions of a single cell, sensory organ precursor (SOP) cell. The number of macrochaetes on drosophila body corresponds to the number of SOP cells. The morphogenesis of macrochaetes comprises three stages, the first two determining a neural fate of the cells. The third stage is cell specialization into components of the bristle organ-neuron, thecogen, tormogen, and trichogen. Development of each bristle commences from segregation of proneural clusters, of 20-30 cells, from the massif of undifferentiated cells of the wing imaginal disc. At this stage, each cluster cell can potentially become a SOP cell. At the second stage, the only SOP cell and its position are determined within each cluster. Finally, two asymmetric divisions of the SOP cell with subsequent differentiation of the daughter cells gives the bristle organ. Several dozens genes are involved in the control of macrochaete morphogenesis. The main component of this system is the proneural genes of achaete-scute complex (AS-C). An increased content of proneural proteins fundamentally distinguished the cells that will follow the neural developmental pathway from the disc epidermal cells. A local AS-C expression, initiated at specified disc sites by specific transcription factors, determines the number and topology of proneural clusters. The expression of AS-C genes, continuing in the cells of the cluster, increases the difference in proneural protein content, first, between the cluster cells and then, between the cluster cells and the single SOP cell, where it reaches the maximum level. This process is provided by both the intracellular regulation of AS-C gene activity and intercellular events mediated via the EGFR and Notch signaling pathways. The third stage in macrochaete morphogenesis comprises two successive asymmetric SOP cell divisions, determining the final specialization. The selector genes, in particular, numb, neuralized, tramtrack, and musashi, play the key role in cell type specification. This review systematizes the data on molecular genetic system controlling drosophila bristle morphogenesis and proposes an integral scheme of its functioning.
在多细胞生物的个体发育过程中，由各种细胞类型组成的特殊空间结构的形成至关重要。果蝇刚毛器官就是一个例子。刚毛（微刚毛和大刚毛）是外部感觉器官，属于外周神经系统的组成部分，起机械感受器的作用。它们相对简单的组织结构仅由四个特化细胞组成，且这些细胞起源相同，这使得大刚毛成为研究细胞分化的便利模型。形成刚毛器官的四个细胞源自单个细胞——感觉器官前体细胞（SOP细胞）的两次连续分裂。果蝇身体上大刚毛的数量与SOP细胞的数量相对应。大刚毛的形态发生包括三个阶段，前两个阶段决定细胞的神经命运。第三阶段是细胞特化为刚毛器官的组成部分——神经元、毛原细胞、膜原细胞和鞘原细胞。每个刚毛的发育始于从翅成虫盘未分化细胞团中分离出由20 - 30个细胞组成的原神经簇。在此阶段，每个簇细胞都有可能成为一个SOP细胞。在第二阶段，确定每个簇内唯一的SOP细胞及其位置。最后，SOP细胞的两次不对称分裂以及随后子细胞的分化产生了刚毛器官。有几十种基因参与大刚毛形态发生的调控。该系统的主要成分是achaete - scute复合体（AS - C）的原神经基因。原神经蛋白含量的增加从根本上区分了将沿着神经发育途径分化的细胞与盘状表皮细胞。由特定转录因子在特定盘状位点启动的局部AS - C表达，决定了原神经簇的数量和拓扑结构。AS - C基因在簇细胞中的持续表达，首先增加了簇细胞之间原神经蛋白含量的差异，然后增加了簇细胞与单个SOP细胞之间的差异，在SOP细胞中原神经蛋白含量达到最高水平。这一过程由AS - C基因活性的细胞内调控以及通过表皮生长因子受体（EGFR）和Notch信号通路介导的细胞间事件共同提供。大刚毛形态发生的第三阶段包括SOP细胞的两次连续不对称分裂，决定最终的特化。选择基因，特别是numb、neuralized、tramtrack和musashi，在细胞类型特化中起关键作用。本综述对控制果蝇刚毛形态发生的分子遗传系统的数据进行了系统化整理，并提出了其功能的整体方案。
