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Gene Review

Gsc  -  goosecoid homeobox

Mus musculus

Synonyms: Homeobox protein goosecoid
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Disease relevance of Gsc

  • The knockout of the homeobox gene goosecoid in the mouse revealed similarities to RA induced embryopathy [1].
  • Further characterization of the goosecoid-overexpressing ES cells revealed that they maintain the expression of stage-specific embryonic antigen-1, and teratomas derived from goosecoid-overexpressing cells show the presence of cell types derived from all three germ layers [2].

Psychiatry related information on Gsc


High impact information on Gsc

  • Its mRNA accumulates as a patch on the side of the epiblast at the site where the primitive streak is first formed. goosecoid-expressing cells are then found at the anterior end of the developing primitive streak, and finally in the anteriormost mesoderm at the tip of the early mouse gastrula, a region that gives rise to the head process [4].
  • We demonstrate further that both the distal and proximal elements are essential for high-level transcription of the gsc gene, specifically in dorsal mesoderm, strongly suggesting that establishment of Spemann's organizer requires synergistic input from activin/BVg1-like and Wnt signaling pathways [5].
  • To understand how integration of these different signaling pathways results in formation of Spemann's organizer, we sought to identify growth factor-responsive elements within the gsc promoter [5].
  • A consequence of all of these signaling pathways, however, seems to be the induction of goosecoid (gsc) gene expression [5].
  • In other cases, such as the activins and goosecoid, the mutant phenotypes force a re-evaluation of models that are based on studies in other vertebrates [6].

Biological context of Gsc

  • The homeobox gene goosecoid (gsc) and the winged-helix gene Hepatic Nuclear Factor-3beta (HNF-3beta) are co-expressed in all three germ layers in the anterior primitive streak and at the rostral end of mouse embryos during gastrulation [7].
  • In this paper, we have tested the possibility of functional synergism or redundancy between these two genes during embryogenesis by generating double-mutant mice for gsc and HNF-3beta [7].
  • These animals were analyzed at birth for skeletal defects and revealed the same phenotype as gsc-/- single mutants [8].
  • Since goosecoid (gsc) shares some domains of expression with cer-l and was shown to be essential for head morphogenesis, we tested its ability to interact genetically with cer-l. With this aim we generated cer-l;gsc double mutants [8].
  • Downregulation of endogenous TFII-I by small inhibitory RNA in P19 cells abolishes the TGFbeta-mediated induction of Gsc [9].

Anatomical context of Gsc

  • We show that, in combination with goosecoid (Gsc), the Bapx1 gene defines the structural components of the murine middle ear [10].
  • Our results also suggest that interaction between gsc and HNF-3beta regulates other signalling molecules required for proper development of the foregut, branchial arches and heart [7].
  • However, the remaining tissues reconstituted Gsc and Shh activity and expressed the ventral forebrain marker Nkx2 [11].
  • In addition to cer-l, anterior visceral endoderm was found to express the transcription factors Lim1, goosecoid and HNF-3beta that are also present in trunk organizer cells [12].
  • We show that RA treatment of mouse gastrula embryos in vitro and of E10.5 embryos in utero led to a rapid but transient down-regulation of goosecoid expression [1].

Associations of Gsc with chemical compounds


Regulatory relationships of Gsc

  • These results indicate that gsc and HNF-3beta interact to regulate Shh expression and consequently dorsal-ventral patterning in the neural tube [7].
  • Similarly, Xenopus embryos with endogenous TFII-I expression downregulated by injection of TFII-I-specific antisense oligonucleotides exhibit decreased Gsc expression [9].

Other interactions of Gsc

  • 5. Gscl is related to Goosecoid ( Gsc ), a gene required for proper craniofacial development in mice [14].
  • The analysis of Nodal-/-;Gsc-/- compound mutant embryos shows that Gsc activity plays no critical role in the acquisition of forebrain characters by Nodal-deficient cells [15].
  • Moreover, twist expression in paraxial mesoderm appears to be dependent on normal T activity, while Shh/vhh-1, goosecoid, mox-1 and cdx-4 are not T dependent [16].
  • Middle ear defects associated with the double knock out mutation of murine goosecoid and Msx1 genes [17].
  • The restriction into rostral (Lhx-7-expressing) and caudal (Gsc-expressing) domains is achieved by cells responding differently according to their proximity to the source of the signal [18].

Analytical, diagnostic and therapeutic context of Gsc


  1. Retinoic acid teratogenicity: the role of goosecoid and BMP-4. Zhu, C.C., Yamada, G., Blum, M. Cell. Mol. Biol. (Noisy-le-grand) (1999) [Pubmed]
  2. goosecoid expression represses Brachyury in embryonic stem cells and affects craniofacial development in chimeric mice. Boucher, D.M., Schäffer, M., Deissler, K., Moore, C.A., Gold, J.D., Burdsal, C.A., Meneses, J.J., Pedersen, R.A., Blum, M. Int. J. Dev. Biol. (2000) [Pubmed]
  3. Nasal and pharyngeal abnormalities caused by the mouse goosecoid gene mutation. Yamada, G., Ueno, K., Nakamura, S., Hanamure, Y., Yasui, K., Uemura, M., Eizuru, Y., Mansouri, A., Blum, M., Sugimura, K. Biochem. Biophys. Res. Commun. (1997) [Pubmed]
  4. Gastrulation in the mouse: the role of the homeobox gene goosecoid. Blum, M., Gaunt, S.J., Cho, K.W., Steinbeisser, H., Blumberg, B., Bittner, D., De Robertis, E.M. Cell (1992) [Pubmed]
  5. Molecular mechanisms of Spemann's organizer formation: conserved growth factor synergy between Xenopus and mouse. Watabe, T., Kim, S., Candia, A., Rothbächer, U., Hashimoto, C., Inoue, K., Cho, K.W. Genes Dev. (1995) [Pubmed]
  6. Early mouse development: lessons from gene targeting. St-Jacques, B., McMahon, A.P. Curr. Opin. Genet. Dev. (1996) [Pubmed]
  7. Goosecoid and HNF-3beta genetically interact to regulate neural tube patterning during mouse embryogenesis. Filosa, S., Rivera-Pérez, J.A., Gómez, A.P., Gansmuller, A., Sasaki, H., Behringer, R.R., Ang, S.L. Development (1997) [Pubmed]
  8. Goosecoid and cerberus-like do not interact during mouse embryogenesis. Borges, A.C., Marques, S., Belo, J.A. Int. J. Dev. Biol. (2002) [Pubmed]
  9. Positive and negative regulation of the transforming growth factor beta/activin target gene goosecoid by the TFII-I family of transcription factors. Ku, M., Sokol, S.Y., Wu, J., Tussie-Luna, M.I., Roy, A.L., Hata, A. Mol. Cell. Biol. (2005) [Pubmed]
  10. Bapx1 regulates patterning in the middle ear: altered regulatory role in the transition from the proximal jaw during vertebrate evolution. Tucker, A.S., Watson, R.P., Lettice, L.A., Yamada, G., Hill, R.E. Development (2004) [Pubmed]
  11. The morphogenetic role of midline mesendoderm and ectoderm in the development of the forebrain and the midbrain of the mouse embryo. Camus, A., Davidson, B.P., Billiards, S., Khoo, P., Rivera-Pérez, J.A., Wakamiya, M., Behringer, R.R., Tam, P.P. Development (2000) [Pubmed]
  12. Cerberus-like is a secreted factor with neutralizing activity expressed in the anterior primitive endoderm of the mouse gastrula. Belo, J.A., Bouwmeester, T., Leyns, L., Kertesz, N., Gallo, M., Follettie, M., De Robertis, E.M. Mech. Dev. (1997) [Pubmed]
  13. The one-eyed pinhead gene functions in mesoderm and endoderm formation in zebrafish and interacts with no tail. Schier, A.F., Neuhauss, S.C., Helde, K.A., Talbot, W.S., Driever, W. Development (1997) [Pubmed]
  14. Goosecoid-like (Gscl), a candidate gene for velocardiofacial syndrome, is not essential for normal mouse development. Saint-Jore, B., Puech, A., Heyer, J., Lin, Q., Raine, C., Kucherlapati, R., Skoultchi, A.I. Hum. Mol. Genet. (1998) [Pubmed]
  15. Absence of Nodal signaling promotes precocious neural differentiation in the mouse embryo. Camus, A., Perea-Gomez, A., Moreau, A., Collignon, J. Dev. Biol. (2006) [Pubmed]
  16. Effects of the TWis mutation on notochord formation and mesodermal patterning. Conlon, F.L., Wright, C.V., Robertson, E.J. Mech. Dev. (1995) [Pubmed]
  17. Middle ear defects associated with the double knock out mutation of murine goosecoid and Msx1 genes. Kuratani, S., Satokata, I., Blum, M., Komatsu, Y., Haraguchi, R., Nakamura, S., Suzuki, K., Kosai, K., Maas, R., Yamada, G. Cell. Mol. Biol. (Noisy-le-grand) (1999) [Pubmed]
  18. Fgf-8 determines rostral-caudal polarity in the first branchial arch. Tucker, A.S., Yamada, G., Grigoriou, M., Pachnis, V., Sharpe, P.T. Development (1999) [Pubmed]
  19. Goosecoid is not an essential component of the mouse gastrula organizer but is required for craniofacial and rib development. Rivera-Pérez, J.A., Mallo, M., Gendron-Maguire, M., Gridley, T., Behringer, R.R. Development (1995) [Pubmed]
  20. Targeted mutation of the murine goosecoid gene results in craniofacial defects and neonatal death. Yamada, G., Mansouri, A., Torres, M., Stuart, E.T., Blum, M., Schultz, M., De Robertis, E.M., Gruss, P. Development (1995) [Pubmed]
  21. Novel expression of the goosecoid transcription factor in the embryonic mouse heart. Conway, S.J. Mech. Dev. (1999) [Pubmed]
  22. Molecular cloning of the human homeobox gene goosecoid (GSC) and mapping of the gene to human chromosome 14q32.1. Blum, M., De Robertis, E.M., Kojis, T., Heinzmann, C., Klisak, I., Geissert, D., Sparkes, R.S. Genomics (1994) [Pubmed]
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