The basic helix-loop-helix transcription factor capsulin controls spleen organogenesis.
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.
Lu
J
J
Departments of Molecular Biology and Pathology, University of Texas Southwestern Medical Center at Dallas, 75235-9148, USA.
Chang
P
P
Richardson
J A
JA
Gan
L
L
Weiler
H
H
Olson
E N
EN
D000818:Animals; D017209:Apoptosis; D051792:Basic Helix-Loop-Helix Proteins; D005260:Female; D020869:Gene Expression Profiling; D017930:Genes, Reporter / Q000235:genetics; D018257:Helix-Loop-Helix Motifs; D006579:Heterozygote; D018398:Homeodomain Proteins / Q000235:genetics / Q000502:physiology; D006720:Homozygote; D017403:In Situ Hybridization; D020287:In Situ Nick-End Labeling; D007763:Lac Operon / Q000235:genetics; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008817:Mice, Mutant Strains; D015513:Oncogene Proteins / Q000235:genetics / Q000502:physiology; D010641:Phenotype; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D013154:Spleen / Q000002:abnormalities / Q000166:cytology / Q000196:embryology* / Q000378:metabolism*; D014157:Transcription Factors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
D051792:Basic Helix-Loop-Helix Proteins; D018398:Homeodomain Proteins; D015513:Oncogene Proteins; D012333:RNA, Messenger; D014157:Transcription Factors; C107965:Nkx3-2 protein, mouse; C491825:TCF21 protein, human; C112923:Tcf21 protein, mouse; C487378:Tlx1 protein, mouse