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

• This is suggested to be essential defects for olfaction. gsc mutant mice also show several pharyngeal phenotypes, including defects in the pharyngeal muscles and the pharyngeal mucosa [3].

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

• Retinoic acid teratogenicity: the role of goosecoid and BMP-4 [1].
• Exposure to lithium, a dorsalizing agent, leads to the ectopic induction and maintenance of gsc expression in wild-type embryos [13].

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

• Transplantation experiments suggest that the ovary does not provide gsc function to rescue gastrulation defects [19].
• To investigate the role of goosecoid in embryonic development, we have inactivated the gene by gene targeting to generate mice mutant for the goosecoid gene [20].
• In order to determine whether gsc is similarly involved in heart morphogenesis, in situ hybridization and RT-PCR were used to detect gsc expression in the embryonic mouse heart [21].
• Molecular cloning of the human homeobox gene goosecoid (GSC) and mapping of the gene to human chromosome 14q32.1 [22].

References