Changes in global gene expression patterns during development and maturation of the rat kidney

We set out to define patterns of gene expression during kidney organogenesi s by using high-density DNA array technology. Expression analysis of 8,740 rat genes revealed five discrete patterns or groups of gene expression duri ng nephrogenesis. Group 1 consisted of genes with very high expression in t he early embryonic kidney, many with roles in protein translation and DNA r eplication. Group 2 consisted of genes that peaked in midembryogenesis and contained many transcripts specifying proteins of the extracellular matrix. Many additional transcripts allied with groups 1 and 2 had known or propos ed roles in kidney development and included LIM1, pool, GFRA1, WT1, BCL2, H omeobox protein All, timeless, pleiotrophin, HGF, HNF3, BMP4, TGF-alpha, TG F-beta2, IGF-II, met. FGF7, BMP4, and ganglioside-GD3. Group 3 consisted of transcripts that peaked in the neonatal period and contained a number of r etrotransposon RNAs. Group 4 contained genes that steadily increased in rel ative expression levels throughout development, including many genes involv ed in energy metabolism and transport. Group 5 consisted of genes with rela tively low levels of expression throughout embryogenesis but with markedly higher levels in the adult kidney; this group included a heterogeneous mix of transporters, detoxification enzymes, and oxidative stress genes. The da ta suggest that the embryonic kidney is committed to cellular proliferation and morphogenesis early on, followed sequentially by extracellular matrix deposition and acquisition of markers of terminal differentiation. The neon atal burst of retrotransposon mRNA was unexpected and may play a role in a stress response associated with birth. Custom analytical tools were develop ed including "The Equalizer" and "eBlot," which contain improved methods fo r data normalization, significance testing, and data mining.