Bracken Christina M, Mizeracka Karolina, McLaughlin Kelly A
Department of Biology, Tufts University, Medford, Massachusetts 02155, USA.
Dev Dyn. 2008 Jan;237(1):132-44. doi: 10.1002/dvdy.21387.
The Bone morphogenetic proteins (BMPs) mediate a wide range of diverse cellular behaviors throughout development. Previous studies implicated an important role for BMP signaling during the differentiation of the definitive mammalian kidney, the metanephros. In order to examine whether BMP signaling also plays an important role during the patterning of earlier renal systems, we examined the development of the earliest nephric system, the pronephros. Using the amphibian model system Xenopus laevis, in combination with reagents designed to inhibit BMP signaling during specific stages of nephric development, we revealed an evolutionarily conserved role for this signaling pathway during renal morphogenesis. Our results demonstrate that conditional BMP inhibition after specification of the pronephric anlagen is completed, but prior to the onset of morphogenesis and differentiation of renal tissues, results in the severe malformation of both the pronephric duct and tubules. Importantly, the effects of BMP signaling on the developing nephron during this developmental window are specific, only affecting the developing duct and tubules, but not the glomus. These data, combined with previous studies examining metanephric development in mice, provide further support that BMP functions to mediate morphogenesis of the specified renal field during vertebrate embryogenesis. Specifically, BMP signaling is required for the differentiation of two types of nephric structures, the pronephric tubules and duct.
骨形态发生蛋白(BMPs)在整个发育过程中介导多种不同的细胞行为。先前的研究表明BMP信号在哺乳动物终末肾(后肾)的分化过程中起重要作用。为了研究BMP信号在早期肾系统模式形成过程中是否也发挥重要作用,我们研究了最早的肾系统——前肾的发育。利用非洲爪蟾(Xenopus laevis)两栖动物模型系统,结合旨在在肾发育的特定阶段抑制BMP信号的试剂,我们揭示了该信号通路在肾形态发生过程中具有进化保守作用。我们的结果表明,在前肾原基特化完成后,但在肾组织形态发生和分化开始之前进行条件性BMP抑制,会导致前肾管和肾小管严重畸形。重要的是,在此发育窗口期间BMP信号对发育中的肾单位的影响是特异性的,仅影响发育中的管道和小管,而不影响肾小球。这些数据与先前研究小鼠后肾发育的研究相结合,进一步支持了BMP在脊椎动物胚胎发育过程中发挥作用介导特定肾区形态发生的观点。具体而言,BMP信号是两种肾结构——前肾小管和前肾管分化所必需的。