The signals that drive kidney development: A view from the fly eye

Purpose of review: Development of the mammalian kidney is a complex process involving numerous signals and signaling pathways. Other complex tissues have benefited enormously from studies in lower, simpler organisms. The present review provides an update on what we have learned from the fruitfly Drosophila melanogaster, and argues that Drosophila is an important but under-utilized organism for study of renal development. Recent findings: The Malpighian tubules provide renal function to the fly. These require a number of signaling pathways for their development that are also seen in vertebrate kidney development, including the Notch, Ras, and Wnt signaling pathways, as well as nuclear factors such as Krüppel and Cut/Cux-1. Many of these factors are shared between early Malpighian tubule development and ureteric bud formation. The Ret signaling receptor, which is central to mammarian renal development, is poorly understood in flies, although its expression pattern is intriguing. Surprisingly, other signaling factors such as Neph-1, Pax2, and Wilms' tumor suppressor-1 appear to work within later fly retinal development, providing a surprising link between these two disparate tissues. Summary: Drosophila offers a powerful palate of tools for dissecting developmental processes. Importantly, these tools can often be examined at the level of single cells, permitting us to address issues of differentiation with high resolution. If we are to take full advantage of Drosophila, however, then we must target specific issues and gain a better understanding of the details of Malpighian tubule development.