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Gene Review

Tcf21  -  transcription factor 21

Mus musculus

Synonyms: Capsulin, Epicardin, Pod-1, Pod1, Podocyte-expressed 1, ...
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Disease relevance of Tcf21


High impact information on Tcf21

  • 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 [4].
  • The basic helix-loop-helix transcription factor capsulin controls spleen organogenesis [4].
  • Capsulin is also expressed in the mesothelium that gives rise to the spleen [4].
  • Additionally, we demonstrate that while Nkx3.2 and Pod1 control spleen development via separate pathways, Pbx1 genetically regulates key players in both pathways, and thus emerges as a central hierarchical co-regulator in spleen genesis [5].
  • In db/db mice at the normoalbuminuric stage, hypoxia-inducible factor-1alpha (HIF-1alpha), ephrin B2, glomerular epithelial protein 1, and Pod-1, which play key roles in glomerulogenesis, were already upregulated in parallel with an alteration of genes related to glucose metabolism, lipid metabolism, and oxidative stress [1].

Biological context of Tcf21

  • These results indicate that epicardin/capsulin/Pod-1 functions as a negative regulator of differentiation of myoblasts through transcription in at least two distinct steps, cell growth arrest and lineage-specific differentiation [6].
  • Epicardin/capsulin/Pod-1, expressed in skeletal myoblasts within brachial arches and in the condensing mesenchyme, is a member of the basic helix-loop-helix (bHLH) transcription factor family that is involved in various cell differentiation processes [6].
  • Combined with gene expression profiling, this method was used to identify differentially expressed genes in glomeruli from Pod1 knockout (KO) mice that die in the perinatal period with multiple renal defects [7].
  • We have identified a novel bHLH protein, named Pod-1, that belongs to a recently-described subfamily of bHLH proteins that have essential roles in the embryonic development of mesodermal tissues [8].
  • Histologic, immunohistochemical, and in situ hybridization analysis of the resulting chimeric offspring demonstrated both cell autonomous and non-cell autonomous roles for Pod1 in the differentiation of specific renal cell lineages that include peritubular interstitial cells and pericytes [9].

Anatomical context of Tcf21

  • Moreover, terminal differentiation of C2C12 myoblasts was inhibited by exogenous introduction of epicardin/capsulin/Pod-1 [6].
  • Pod1 is required in stromal cells for glomerulogenesis [9].
  • Capsulin was shown to be expressed as early as 9.5 days of mouse development, with expression in mesodermal cells that are progenitors of the epicardium and the coronary arteries [10].
  • epicardin: A novel basic helix-loop-helix transcription factor gene expressed in epicardium, branchial arch myoblasts, and mesenchyme of developing lung, gut, kidney, and gonads [11].
  • To further dissect the cellular function of Pod1 during kidney development, chimeric mice were generated through aggregations of null Pod1 embryonic stem cells and murine embryos ubiquitously expressing enhanced green fluorescent protein (GFP) [9].

Associations of Tcf21 with chemical compounds

  • Chromatin immunoprecipitation assay showed that epicardin/capsulin/Pod-1 was physically associated with the muscle creatine kinase promoter in vivo [6].
  • With this approach, 3986 genes that are differently expressed between glomeruli from Pod1 KO and wild-type mice were identified, including a four-fold reduction of alpha 8 integrin mRNA in glomeruli from Pod1 KO mice that was confirmed by immunostaining [7].

Other interactions of Tcf21

  • Kreisler acts during the final stages of glomerular development-the transition between the capillary loop and mature stages-and downstream of the Pod1 basic domain helix-loop-helix transcription factor [12].

Analytical, diagnostic and therapeutic context of Tcf21

  • In situ hybridization studies revealed strong epicardin expression in murine embryos at 9.5 days postcoitum (dpc) in a region of the septum transversum at the base of the heart known as the proepicardial organ [11].
  • Northern blot analysis showed that POD-1/Capsulin are preferentially expressed in human vascular smooth muscle cells, and are enriched in mouse heart, kidney, testis, spleen, and lung [13].


  1. Altered Gene Expression Related to Glomerulogenesis and Podocyte Structure in Early Diabetic Nephropathy of db/db Mice and Its Restoration by Pioglitazone. Makino, H., Miyamoto, Y., Sawai, K., Mori, K., Mukoyama, M., Nakao, K., Yoshimasa, Y., Suga, S. Diabetes (2006) [Pubmed]
  2. Transgene of MIF induces podocyte injury and progressive mesangial sclerosis in the mouse kidney. Sasaki, S., Nishihira, J., Ishibashi, T., Yamasaki, Y., Obikane, K., Echigoya, M., Sado, Y., Ninomiya, Y., Kobayashi, K. Kidney Int. (2004) [Pubmed]
  3. Math6 expression during kidney development and altered expression in a mouse model of glomerulosclerosis. Ross, M.D., Martinka, S., Mukherjee, A., Sedor, J.R., Vinson, C., Bruggeman, L.A. Dev. Dyn. (2006) [Pubmed]
  4. The basic helix-loop-helix transcription factor capsulin controls spleen organogenesis. Lu, J., Chang, P., Richardson, J.A., Gan, L., Weiler, H., Olson, E.N. Proc. Natl. Acad. Sci. U.S.A. (2000) [Pubmed]
  5. A Pbx1-dependent genetic and transcriptional network regulates spleen ontogeny. Brendolan, A., Ferretti, E., Salsi, V., Moses, K., Quaggin, S., Blasi, F., Cleary, M.L., Selleri, L. Development (2005) [Pubmed]
  6. Basic helix-loop-helix transcription factor epicardin/capsulin/Pod-1 suppresses differentiation by negative regulation of transcription. Funato, N., Ohyama, K., Kuroda, T., Nakamura, M. J. Biol. Chem. (2003) [Pubmed]
  7. Rapid isolation of glomeruli coupled with gene expression profiling identifies downstream targets in Pod1 knockout mice. Cui, S., Li, C., Ema, M., Weinstein, J., Quaggin, S.E. J. Am. Soc. Nephrol. (2005) [Pubmed]
  8. Pod-1, a mesoderm-specific basic-helix-loop-helix protein expressed in mesenchymal and glomerular epithelial cells in the developing kidney. Quaggin, S.E., Vanden Heuvel, G.B., Igarashi, P. Mech. Dev. (1998) [Pubmed]
  9. Pod1 is required in stromal cells for glomerulogenesis. Cui, S., Schwartz, L., Quaggin, S.E. Dev. Dyn. (2003) [Pubmed]
  10. Cloning of capsulin, a basic helix-loop-helix factor expressed in progenitor cells of the pericardium and the coronary arteries. Hidai, H., Bardales, R., Goodwin, R., Quertermous, T., Quertermous, E.E. Mech. Dev. (1998) [Pubmed]
  11. epicardin: A novel basic helix-loop-helix transcription factor gene expressed in epicardium, branchial arch myoblasts, and mesenchyme of developing lung, gut, kidney, and gonads. Robb, L., Mifsud, L., Hartley, L., Biben, C., Copeland, N.G., Gilbert, D.J., Jenkins, N.A., Harvey, R.P. Dev. Dyn. (1998) [Pubmed]
  12. The mouse Kreisler (Krml1/MafB) segmentation gene is required for differentiation of glomerular visceral epithelial cells. Sadl, V., Jin, F., Yu, J., Cui, S., Holmyard, D., Quaggin, S., Barsh, G., Cordes, S. Dev. Biol. (2002) [Pubmed]
  13. Molecular characterization of mesoderm-restricted basic helix-loop-helix protein, POD-1/Capsulin. Miyagishi, M., Nakajima, T., Fukamizu, A. Int. J. Mol. Med. (2000) [Pubmed]
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