Department of Pathology and Laboratory Medicine, Robert Wood Johnson Medical School, University of Medicine and Dentistry of New Jersey, Piscataway, New Jersey 08854-8020, USA.
Dev Dyn. 2012 Apr;241(4):759-69. doi: 10.1002/dvdy.23749. Epub 2012 Feb 14.
In this study we examined Roundabout signaling in the Drosophila embryonic hindgut.
Slit and its receptors Roundabout (Robo) and Roundabout 2 (Robo2) localize to discrete regions in the hindgut epithelium and surrounding visceral mesoderm. Loss of robo, robo2 or slit did not disrupt overall hindgut patterning. However, slit and robo mutants showed a decrease in microvillus length on the boundary cells of the hindgut epithelium. Rescue and overexpression analysis revealed that robo is specifically required in the visceral mesoderm for correct microvillus length in the underlying hindgut epithelium. Expression of robo in the visceral mesoderm of robo mutant embryos restored normal microvillus length, while overexpression of robo resulted in an increase in microvillus length. Microvillus length was also increased in robo2 mutants suggesting that robo2 may antagonize robo function in the hindgut.
Together, these results establish a novel, dose-dependent role for Robo in regulating microvilli growth and provide in vivo evidence for the role of the visceral mesoderm in controlling morphological changes in the underlying intestinal epithelium.
在这项研究中，我们研究了果蝇胚胎后肠中的 Roundabout 信号通路。
Slit 及其受体 Roundabout（Robo）和 Roundabout 2（Robo2）定位于后肠上皮和周围内脏中胚层的离散区域。Robo、Robo2 或 Slit 的缺失并未破坏后肠的整体模式。然而，Slit 和 Robo 突变体在后肠上皮的边界细胞上表现出微绒毛长度的减少。挽救和过表达分析表明，Robo 在后肠内脏中胚层中特异性地需要维持后肠上皮中正确的微绒毛长度。在 Robo 突变体胚胎的内脏中胚层中表达 Robo 可恢复正常的微绒毛长度，而过表达 Robo 则导致微绒毛长度增加。Robo2 突变体中的微绒毛长度也增加，表明 Robo2 可能在后肠中拮抗 Robo 的功能。
这些结果确立了 Robo 在调节微绒毛生长中的新的、剂量依赖性作用，并为内脏中胚层在控制下伏肠上皮形态变化中的作用提供了体内证据。
