Kavaler J, Fu W, Duan H, Noll M, Posakony J W
Department of Biology, University of California San Diego, La Jolla, CA 92093-0349, USA.
Development. 1999 May;126(10):2261-72. doi: 10.1242/dev.126.10.2261.
The adult peripheral nervous system of Drosophila includes a complex array of mechanosensory organs (bristles) that cover much of the body surface of the fly. The four cells (shaft, socket, sheath, and neuron) which compose each of these organs adopt distinct fates as a result of cell-cell signaling via the Notch (N) pathway. However, the specific mechanisms by which these cells execute their conferred fates are not well understood. Here we show that D-Pax2, the Drosophila homolog of the vertebrate Pax2 gene, has an essential role in the differentiation of the shaft cell. In flies bearing strong loss-of-function mutations in the shaven function of D-Pax2, shaft structures specifically fail to develop. Consistent with this, we find that D-Pax2 protein is expressed in all cells of the bristle lineage during the mitotic (cell fate specification) phase of bristle development, but becomes sharply restricted to the shaft and sheath cells in the post-mitotic (differentiative) phase. Two lines of evidence described here indicate that D-Pax2 expression and function is at least in part downstream of cell fate specification mechanisms such as N signaling. First, we find that the lack of late D-Pax2 expression in the socket cell (the sister of the shaft cell) is controlled by N pathway activity; second, we find that loss of D-Pax2 function is epistatic to the socket-to-shaft cell fate transformation caused by reduced N signaling. Finally, we show that misexpression of D-Pax2 is sufficient to induce the production of ectopic shaft structures. From these results, we propose that D-Pax2 is a high-level transcriptional regulator of the shaft cell differentiation program, and acts downstream of the N signaling pathway as a specific link between cell fate determination and cell differentiation in the bristle lineage.
果蝇的成年外周神经系统包含一系列复杂的机械感觉器官（刚毛），覆盖了果蝇身体表面的大部分区域。构成这些器官的四个细胞（轴细胞、套细胞、鞘细胞和神经元）通过Notch（N）信号通路进行细胞间信号传导，从而获得不同的命运。然而，这些细胞执行其既定命运的具体机制尚不清楚。在此，我们表明，果蝇中与脊椎动物Pax2基因同源的D-Pax2，在轴细胞的分化中起着至关重要的作用。在D-Pax2的“剃须”功能发生严重功能丧失突变的果蝇中，轴结构特别无法发育。与此一致的是，我们发现D-Pax2蛋白在刚毛发育的有丝分裂（细胞命运决定）阶段，在刚毛谱系的所有细胞中表达，但在有丝分裂后（分化）阶段，急剧局限于轴细胞和鞘细胞。本文所述的两条证据表明，D-Pax2的表达和功能至少部分处于细胞命运决定机制（如N信号传导）的下游。首先，我们发现套细胞（轴细胞的姐妹细胞）中D-Pax2的晚期表达缺失受N信号通路活性的控制；其次，我们发现D-Pax2功能的丧失对于由N信号传导减少引起的套细胞到轴细胞命运转变具有上位性。最后，我们表明D-Pax2的错误表达足以诱导异位轴结构的产生。从这些结果中，我们提出D-Pax2是轴细胞分化程序的高级转录调节因子，并作为刚毛谱系中细胞命运决定和细胞分化之间的特定联系，在N信号通路的下游发挥作用。
