Molecular Regulation of Pronephric Development

University Of Texas At Austin, Austin TX

Investigators

Abstract

Previous experiments have demonstrated the requirement for a number of genes for normal kidney development in mammals. However, little is known about why these genes are important, and even less is known how they interact to firstly specify, and then guide the differentiation of the different kidney components. The frog embryo is particularly well suited to investigating these types of questions, as a single gene can be overexpressed simply by microinjecting embryos with an mRNA encoding the gene product of interest. The embryo is then raised for three days until its kidneys are functional and the effect of the additional gene expression analyzed by looking at kidney structure. In the present proposal experiments are described that will investigate key early steps in the patterning of the kidney precursor region. It has been demonstrated that two transcription factors, Xlim-1 and XPax-8, participate in the establishment of the kidney region shortly after gastrulation. The experiments outlined here will investigate how these two different proteins interact to achieve this effect. The experiments will also investigate how these genes regulate, and are in turn regulated by, the downstream effector gene Xenopus WT1. These experiments will build on the existing models of how organs are established during embryonic development by analyzing the molecular interactions controlling this event. As all vertebrate kidneys use similar genetic pathways the results will be of relevance not only to developmental biologists, but also to researchers interested in establishing model systems in which to study human kidney defects.