The basic helix-loop-helix transcription factor capsulin controls spleen organogenesis. Proc Natl Acad Sci U S A 2000 Aug 15;97(17):9525-30
Date
08/16/2000Pubmed ID
10944221Pubmed Central ID
PMC16898DOI
10.1073/pnas.97.17.9525Scopus ID
2-s2.0-0034662960 (requires institutional sign-in at Scopus site) 111 CitationsAbstract
Formation of numerous internal organs involves reciprocal epithelial-mesenchymal signaling and subsequent patterning and growth of the organ primordium. Capsulin is a basic helix-loop-helix transcription factor expressed in mesenchymal cells that encapsulate the epithelial primordia of internal organs, including the kidney and lung, as well as the epicardium, which gives rise to the coronary arteries. Capsulin is also expressed in the mesothelium that gives rise to the spleen. We demonstrate that mice homozygous for a capsulin null mutation fail to form a spleen. The homeobox genes Hox11 and Bapx1, shown previously to be essential regulators of spleen organogenesis, and a lacZ reporter introduced into the capsulin locus, were expressed in the early splenic primordium, derived from the splanchnic mesoderm, of homozygous mutant embryos. However, this primordium failed to develop beyond an initial group of precursor cells and underwent rapid apoptosis. The phenotype of capsulin mutant mice demonstrates that capsulin acts within a subpopulation of splanchnic mesodermal cells to control an essential early step in spleen organogenesis that is likely to represent a point of regulatory convergence of the capsulin, Hox11, and Bapx1 genes.
Author List
Lu J, Chang P, Richardson JA, Gan L, Weiler H, Olson ENAuthor
Hartmut Weiler PhD Associate Professor in the Physiology department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsApoptosis
Basic Helix-Loop-Helix Transcription Factors
Female
Gene Expression Profiling
Genes, Reporter
Helix-Loop-Helix Motifs
Heterozygote
Homeodomain Proteins
Homozygote
In Situ Hybridization
In Situ Nick-End Labeling
Lac Operon
Male
Mice
Mice, Knockout
Mice, Mutant Strains
Oncogene Proteins
Phenotype
RNA, Messenger
Spleen
Transcription Factors
