Patterning the embryonic kidney: BMP signaling mediates the differentiation of the pronephric tubules and duct in Xenopus laevis

Abstract

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. Developmental Dynamics 237:132-144, 2008.

A dual requirement for Iroquois genes duringXenopuskidney development

“…A recent report showed that blocking this pathway during Xenopus neurula stages impaired pronephros formation (Bracken et al, 2008). These results resemble those observed by reducing Irx function.…”

“…Thus, one possible mechanism of action of Irx proteins could be to 3205 RESEARCH ARTICLE Irx genes in Xenopus kidney development upregulate Bmp signalling, which is known to participate at many steps during vertebrate kidney formation (Cain et al, 2008). Consistent with this idea, the reduction of Bmp signalling during Xenopus neurula stages causes defects similar to those produced by Irx gene impairment (Bracken et al, 2008). Furthermore, we show that increasing Bmp signalling partially rescue the kidney defects observed in Irx morphant and that Bmp7 expression is downregulated in Irx-deficient embryos.…”

Reprogramming cell fate to pluripotency: the decision-making signalling pathways

“…Thus, the induction of the opposite process (MET), characterized by the upregulation of ephitelial junctional components and morphological transformation into ephitelial-like colonies, seems to be a crucial step in the reprogramming process. It was suggested that BMP signal synergized with the Yamanaka factors to induce the expression of miR-200 family, that are well known to promote MET and reprogramming, also in absence of BMP signalling (Bracken et al, 2008;Gregory et al, 2008;Korpal et al, 2008) and to inhibit loss of pluripotency of mESCs in differentiating conditions (Lin et al, 2009).…”

In vitro organogenesis from undifferentiated cells in Xenopus

“…Therefore, XC3H-3b may regulate tubulogenesis by means of JNK/MAPK signaling during Xenopus pronephros development. FGF and BMP are also reported to regulate pronephros development (Urban et al, 2006;Bracken et al, 2008). The FGF signal is necessary for the condensation and transition of the nephric mesenchyme during early tubulogenesis, and the BMP signal is suggested to regulate the differentiation of the tubule and duct.…”