Credit: Courtesy of Eric Olson, University of Texas Southwestern Medical Center, USA. Reproduced with permission from PNAS, © 2000 National Academy of Sciences.

The identification of a gene required for the development of a specific vertebrate organ is a big event in developmental biology — and one of lasting significance. With a new mouse knockout, Lu et al. have shown that the gene capsulin is necessary for spleen development.

Capsulin is a basic helix–loop–helix (bHLH) transcription factor expressed in mesenchymal cells during the early development of the heart, gut, kidneys and lungs (picture shows capsulin expression at embryonic day 13.5). In the capsulin mutants made by Lu et al., the initial stages of spleen development seem normal but the subsequent expansion of splenic precursor cells does not occur. And the end result? No spleen.

Two other genes, Hox11 and Bapx1 , have a similar expression pattern and a similar knockout phenotype to capsulin. Both genes encode homeobox transcription factors. Lu et al. conclude that capsulin, Hox11 and Bapx1 may work together within the mesenchyme to regulate epithelial–mesenchymal interactions during the early development of the spleen. They also point out that cooperation between bHLH and homeobox proteins has been reported in pituitary development, and may represent a common developmental mechanism.

Knockouts in capsulin also have severe defects in the lung and the kidney — although the homozygotes survive to term, they die within minutes of birth because of breathing problems. This phenotype was reported last year in an independent capsulin mouse knockout made by Quaggin et al ., who also noted defects in branching morphogenesis in lung and kidney. So although the most severe organ defect in the capsulin mutant is the absent spleen, further analysis of capsulin and its cooperation with other transcription factors will have wide-ranging relevance to organogenesis in vertebrates.