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Gene Review

Fst  -  follistatin

Mus musculus

Synonyms: AL033346, Activin-binding protein, FS, Follistatin
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Disease relevance of Fst


High impact information on Fst

  • We show that deacetylase inhibitors increase the size of myofibers in dystrophin-deficient (MDX) and alpha-sarcoglycan (alpha-SG)-deficient mice by inducing the expression of the myostatin antagonist follistatin in satellite cells [5].
  • In the mouse, follistatin messenger RNA is first detected in the deciduum (on embryonic day 5.5), and later in the developing hindbrain, somites, vibrissae, teeth, epidermis and muscle [6].
  • We find that follistatin-deficient mice are retarded in their growth, have decreased mass of the diaphragm and intercostal muscles, shiny taut skin, skeletal defects of the hard palate and the thirteenth pair of ribs, their whisker and tooth development is abnormal, they fail to breathe, and die within hours of birth [6].
  • A binding protein for activin was purified from rat ovary and was identical to follistatin, a specific inhibitor of FSH release [7].
  • Mice lacking functional GDF11 have more progenitors and neurons in the OE, whereas mice lacking follistatin, a GDF11 antagonist, show dramatically decreased neurogenesis [8].

Chemical compound and disease context of Fst

  • In the CSF of patients with meningitis, the concentration of FS was correlated with total protein (P<0.005) and lactate concentrations (P<0.05), but not with leukocyte counts, interval between onset of disease and CSF analysis, or clinical outcome [9].

Biological context of Fst


Anatomical context of Fst


Associations of Fst with chemical compounds

  • Current studies indicate that the heparin binding sequence is essential for the ability of FS to inhibit autocrine activin but is not sufficient to confer this activity on FSTL3 [15].
  • Expression of the activin-binding protein follistatin is altered by the induction of differentiation of P19 EC and ES cells by several factors, including retinoic acid [16].
  • Exogenous follistatin inhibited the allergen-specific Th2 immune response in mediastinal lymph nodes and mucus production in the lung [17].
  • Follistatin induction by nitric oxide through cyclic GMP: a tightly regulated signaling pathway that controls myoblast fusion [18].
  • The decline in FS transcript levels in untreated and hCG-treated cells was studied by blocking the transcription with 5 microM actinomycin-D [19].

Physical interactions of Fst


Regulatory relationships of Fst


Other interactions of Fst


Analytical, diagnostic and therapeutic context of Fst


  1. Follistatin is a modulator of gonadal tumor progression and the activin-induced wasting syndrome in inhibin-deficient mice. Cipriano, S.C., Chen, L., Kumar, T.R., Matzuk, M.M. Endocrinology (2000) [Pubmed]
  2. Human testicular germ cell tumours express inhibin subunits, activin receptors and follistatin mRNAs. van Schaik, R.H., Wierikx, C.D., Looijenga, L.H., Oosterhuis, J.W., de Jong, F.H. Br. J. Cancer (1997) [Pubmed]
  3. A secreted tumor-suppressor, mac25, with activin-binding activity. Kato, M.V. Mol. Med. (2000) [Pubmed]
  4. Overexpression of mouse follistatin causes reproductive defects in transgenic mice. Guo, Q., Kumar, T.R., Woodruff, T., Hadsell, L.A., DeMayo, F.J., Matzuk, M.M. Mol. Endocrinol. (1998) [Pubmed]
  5. Functional and morphological recovery of dystrophic muscles in mice treated with deacetylase inhibitors. Minetti, G.C., Colussi, C., Adami, R., Serra, C., Mozzetta, C., Parente, V., Fortuni, S., Straino, S., Sampaolesi, M., Di Padova, M., Illi, B., Gallinari, P., Steink??hler, C., Capogrossi, M.C., Sartorelli, V., Bottinelli, R., Gaetano, C., Puri, P.L. Nat. Med. (2006) [Pubmed]
  6. Multiple defects and perinatal death in mice deficient in follistatin. Matzuk, M.M., Lu, N., Vogel, H., Sellheyer, K., Roop, D.R., Bradley, A. Nature (1995) [Pubmed]
  7. Activin-binding protein from rat ovary is follistatin. Nakamura, T., Takio, K., Eto, Y., Shibai, H., Titani, K., Sugino, H. Science (1990) [Pubmed]
  8. Autoregulation of neurogenesis by GDF11. Wu, H.H., Ivkovic, S., Murray, R.C., Jaramillo, S., Lyons, K.M., Johnson, J.E., Calof, A.L. Neuron (2003) [Pubmed]
  9. Follistatin (FS) in human cerebrospinal fluid and regulation of FS expression in a mouse model of meningitis. Michel, U., Ebert, S., Schneider, O., Shintani, Y., Bunkowski, S., Smirnov, A., Stringaris, A., Gerber, J., Brück, W., Nau, R. Eur. J. Endocrinol. (2000) [Pubmed]
  10. A follistatin-like gene, mac25, may act as a growth suppressor of osteosarcoma cells. Kato, M.V., Sato, H., Tsukada, T., Ikawa, Y., Aizawa, S., Nagayoshi, M. Oncogene (1996) [Pubmed]
  11. Activin regulates betaA-subunit and activin receptor messenger ribonucleic acid and cellular proliferation in activin-responsive testicular tumor cells. Di Simone, N., Hall, H.A., Welt, C., Schneyer, A.L. Endocrinology (1998) [Pubmed]
  12. Modulation of activin/bone morphogenetic protein signaling by follistatin is required for the morphogenesis of mouse molar teeth. Wang, X.P., Suomalainen, M., Jorgez, C.J., Matzuk, M.M., Wankell, M., Werner, S., Thesleff, I. Dev. Dyn. (2004) [Pubmed]
  13. Activin disrupts epithelial branching morphogenesis in developing glandular organs of the mouse. Ritvos, O., Tuuri, T., Erämaa, M., Sainio, K., Hildén, K., Saxén, L., Gilbert, S.F. Mech. Dev. (1995) [Pubmed]
  14. Expression of activin subunits, activin receptors and follistatin in postimplantation mouse embryos suggests specific developmental functions for different activins. Feijen, A., Goumans, M.J., van den Eijnden-van Raaij, A.J. Development (1994) [Pubmed]
  15. Differential actions of follistatin and follistatin-like 3. Schneyer, A., Sidis, Y., Xia, Y., Saito, S., del Re, E., Lin, H.Y., Keutmann, H. Mol. Cell. Endocrinol. (2004) [Pubmed]
  16. Differential expression of inhibin subunits and follistatin, but not of activin receptor type II, during early murine embryonic development. van den Eijnden-van Raaij, A.J., Feijen, A., Lawson, K.A., Mummery, C.L. Dev. Biol. (1992) [Pubmed]
  17. Follistatin is a candidate endogenous negative regulator of activin A in experimental allergic asthma. Hardy, C.L., O'Connor, A.E., Yao, J., Sebire, K., de Kretser, D.M., Rolland, J.M., Anderson, G.P., Phillips, D.J., O'Hehir, R.E. Clin. Exp. Allergy (2006) [Pubmed]
  18. Follistatin induction by nitric oxide through cyclic GMP: a tightly regulated signaling pathway that controls myoblast fusion. Pisconti, A., Brunelli, S., Di Padova, M., De Palma, C., Deponti, D., Baesso, S., Sartorelli, V., Cossu, G., Clementi, E. J. Cell Biol. (2006) [Pubmed]
  19. Activin-binding protein follistatin messenger ribonucleic acid and secreted protein levels are induced by chorionic gonadotropin in cultured human granulosa-luteal cells. Tuuri, T., Erämaa, M., Hildén, K., Ritvos, O. Endocrinology (1994) [Pubmed]
  20. Follistatin complexes Myostatin and antagonises Myostatin-mediated inhibition of myogenesis. Amthor, H., Nicholas, G., McKinnell, I., Kemp, C.F., Sharma, M., Kambadur, R., Patel, K. Dev. Biol. (2004) [Pubmed]
  21. The activin-binding protein follistatin is expressed in developing murine molar and induces odontoblast-like cell differentiation in vitro. Heikinheimo, K., Bègue-Kirn, C., Ritvos, O., Tuuri, T., Ruch, J.V. J. Dent. Res. (1997) [Pubmed]
  22. Sexually dimorphic regulation of inhibin Beta B in establishing gonadal vasculature in mice. Yao, H.H., Aardema, J., Holthusen, K. Biol. Reprod. (2006) [Pubmed]
  23. Interleukin-1 beta enhances and interferon-gamma suppresses activin A actions by reciprocally regulating activin A and follistatin secretion from bone marrow stromal fibroblasts. Abe, M., Shintani, Y., Eto, Y., Harada, K., Fujinaka, Y., Kosaka, M., Matsumoto, T. Clin. Exp. Immunol. (2001) [Pubmed]
  24. Gdf11 is a negative regulator of chondrogenesis and myogenesis in the developing chick limb. Gamer, L.W., Cox, K.A., Small, C., Rosen, V. Dev. Biol. (2001) [Pubmed]
  25. HtrA1 serine protease inhibits signaling mediated by Tgfbeta family proteins. Oka, C., Tsujimoto, R., Kajikawa, M., Koshiba-Takeuchi, K., Ina, J., Yano, M., Tsuchiya, A., Ueta, Y., Soma, A., Kanda, H., Matsumoto, M., Kawaichi, M. Development (2004) [Pubmed]
  26. Novel factors in regulation of activin signaling. Tsuchida, K., Nakatani, M., Matsuzaki, T., Yamakawa, N., Liu, Z., Bao, Y., Arai, K.Y., Murakami, T., Takehara, Y., Kurisaki, A., Sugino, H. Mol. Cell. Endocrinol. (2004) [Pubmed]
  27. Ontogeny of activin B and follistatin in developing embryonic mouse pancreas: implications for lineage selection. Maldonado, T.S., Kadison, A.S., Crisera, C.A., Grau, J.B., Alkasab, S.L., Longaker, M.T., Gittes, G.K. J. Gastrointest. Surg. (2000) [Pubmed]
  28. Peroxisome proliferator-activated receptor gamma down-regulates follistatin in intestinal epithelial cells through SP1. Necela, B.M., Su, W., Thompson, E.A. J. Biol. Chem. (2008) [Pubmed]
  29. Therapeutic potential of follistatin for colonic inflammation in mice. Dohi, T., Ejima, C., Kato, R., Kawamura, Y.I., Kawashima, R., Mizutani, N., Tabuchi, Y., Kojima, I. Gastroenterology (2005) [Pubmed]
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