Creating an embryonic kidney: The role of bone morphogenetic protein signaling during patterning and differentiation of pronephric tissue in Xenopus laevis

Bone Morphogenetic Proteins (BMPs) mediate diverse developmental processes including embryogenesis, organ morphogenesis as well as regeneration. Although studies in transgenic mice have implicated the necessity of BMPs during later stages of mammalian nephrogenesis, a role during patterning and differentiation of the pronephros, has yet to be identified. In order to address this gap, we examined the effect of BMP mis-regulation on differentiation of the pronephric kidney in Xenopus laevis. Because BMP signaling is required during early developmental events such as axis specification and mesoderm patterning, it is imperative to maintain temporal and spatial control of BMP manipulations. To achieve this, we utilized hormone-inducible constructs designed to either up or down-regulate BMP signaling. Our results show that down-regulation of the BMP pathway leads to undifferentiated and non-functional tubules and duct, but has no effect on glomal development. Interestingly, we noted an increase in expression of the unknown tubule antigen 3G8 in the absence of BMP signaling. Up-regulation of the BMP pathway results in a loss of all nephric markers examined including glomal transcripts. We demonstrate that the effect of BMP down-regulation on the pronephric kidney is not due to a primary effect on general mesoderm development; however this may be the case for BMP up-regulation. Our results further elucidate the molecules involved in creating and patterning the pronephros, a system whose accurate formation is critical for proper development of subsequent nephric structures.