Laser capture-microarray analysis of Lim1 mutant kidney development.

Abstract

The Lim1 gene has essential functions during several stages of kidney development. In particular, a tissue-specific knockout in the early metanephric mesenchyme results in the formation of the earliest nephron precursor, the renal vesicle, but failure of this structure to progress to the next stage, the comma-shaped body. To better understand the molecular nature of this developmental arrest, we used a laser capture microdissection-microarray strategy to examine the perturbed gene expression pattern of the mutant renal vesicles. Among the genes found differently expressed were Chrdl2, an inhibitor of BMP signaling, the proapoptotic factor Bmf, as well as myob5, an atypical myosin that modulates chemokine signaling, and pdgfrl, which is important in epithelial folding. Of particular interest, the microarray data indicated that the Dkk1 gene, which encodes an inhibitor of Wnt signaling, was downregulated ninefold in mutants. This was confirmed by in situ hybridizations. It is interesting to note that Lim1 and Dkk1 mutant mice have striking similarities in phenoytpe. These results suggest that the Dkk1 gene might be a key downstream effector of Lim1 function.