GSC (gene)

Goosecoid homeobox

PDB rendering based on 2dmu.
Available structures
PDB Ortholog search: PDBe, RCSB
Identifiers
Symbols GSC ; SAMS
External IDs OMIM: 138890 MGI: 95841 HomoloGene: 7744 GeneCards: GSC Gene
RNA expression pattern
More reference expression data
Orthologs
Species Human Mouse
Entrez 145258 14836
Ensembl ENSG00000133937 ENSMUSG00000021095
UniProt P56915 Q02591
RefSeq (mRNA) NM_173849 NM_010351
RefSeq (protein) NP_776248 NP_034481
Location (UCSC) Chr 14:
94.77 – 94.77 Mb		 Chr 12:
104.47 – 104.47 Mb
PubMed search

Homeobox protein goosecoid is a protein that in humans is encoded by the GSC gene.[1][2] This gene encodes a member of the bicoid subfamily of the paired (PRD) homeobox family of proteins. The encoded protein acts as a transcription factor and may be autoregulatory. A similar protein in mice plays a role in craniofacial and rib cage development during embryogenesis.[2]

Koller's sickle is the first to express the chick homeobox gene goosecoid (GSC).[3]

Function

The GSC gene defines neural-crest cell-fate specification and contributes to dorsal - ventral patterning. Over activation in Xenopus promotes dorso-anterior migration and dorsalization of mesodermal tissue of the cells along with BMP-4.[4] Conversely, loss-of-functions analysis indirectly prevented head formation in Xenopus [5] and head defects in zebrafish.[6] Although, knock-out studies in mice showed that the GSC gene is not required for gastrulation but there is still reduction of the base of the cranium. A mutation in the GSC gene in Drosophila is lethal.[7]

Gsc gene promotes the formation of Spemann’s Organizer. This organizer prevents BMP-4 from inducing the ectoderm in the future head region of the embryo to become epidermis; it instead allows the future head region to form neural folds, which will eventually turn into the brain and spinal cord. For normal anterior development to occur, Spemann’s organizer cannot express the Xwnt-8 or BMP-4 transcription factors. Gsc directly represses the expression of Xwnt-8 while indirectly repressing BMP-4.[8] The inhibition of Xwnt-8 and BMP-4 ensures that normal anterior development, promoted by Spemann’s organizer, can occur.

The expression of Gsc occurs twice in development, first during gastrulation and second during organogenesis.[9] Gsc is found in high concentrations in the dorsal mesoderm and endoderm during gastrulation. The later expression of Gsc is confined to the head region. In the Xenopus, cells that express Gsc become the pharyngeal endoderm, the head mesoderm, ventral skeletal tissue of the head, and the notocord.[10]

Mutations

A mutation in the GSC gene causes short stature, auditory canal atresia, mandibular hypoplasia, and skeletal abnormalities (SAMS). SAMS was previously thought to be an autosomal-recessive disorder but studies with molecular karyotyping and whole-exome sequencing (WES) has shown otherwise.[11]

Mutations in the Gsc gene can lead to specific phenotypes resulting from the second expression of the Gsc gene during organogenesis. Mice knock-out models of the gene express defects in the tongue, nasal cavity, nasal pits, inner ear, and external auditory meatus.[12] Neonate mice born with this mutation die within 24 hours due to complication with breathing and sucking milk, resulting from the craniofacial abnormalities caused by the mutation. Mutations to the Gsc gene in humans can lead to a condition known as SAMS syndrome, characterized by short stature, auditory canal atresia, mandibular hypoplasia, and skeletal abnormalities.[13][14]

References

  1. ↑ Blum M, De Robertis EM, Kojis T, Heinzmann C, Klisak I, Geissert D, Sparkes RS (Oct 1994). "Molecular cloning of the human homeobox gene goosecoid (GSC) and mapping of the gene to human chromosome 14q32.1". Genomics 21 (2): 388–393. doi:10.1006/geno.1994.1281. PMID 7916327.
  2. 1 2 "Entrez Gene: GSC goosecoid".
  3. ↑ Izpisúa-Belmonte JC, De Robertis EM, Storey KG, Stern CD (1993). "The homeobox gene goosecoid and the origin of organizer cells in the early chick blastoderm". Cell 74 (4): 645–59. doi:10.1016/0092-8674(93)90512-o. PMID 7916659.
  4. ↑ Niehrs C, Keller R, Cho KW, De Robertis EM (1993). "The homeobox gene goosecoid controls cell migration in Xenopus embryos". Cell 72 (4): 491–503. doi:10.1016/0092-8674(93)90069-3. PMID 8095000.
  5. ↑ Steinbeisser H, Fainsod A, Niehrs C, Sasai Y, De Robertis EM (Nov 1995). "The role of gsc and BMP-4 in dorsal-ventral patterning of the marginal zone in Xenopus: a loss-of-function study using antisense RNA". The EMBO Journal 14 (21): 5230–43. PMID 7489713.
  6. ↑ Rivera-Pérez JA, Mallo M, Gendron-Maguire M, Gridley T, Behringer RR (Sep 1995). "Goosecoid is not an essential component of the mouse gastrula organizer but is required for craniofacial and rib development". Development 121 (9): 3005–12. PMID 7555726.
  7. ↑ Goriely A, Stella M, Coffinier C, Kessler D, Mailhos C, Dessain S, Desplan C (May 1996). "A functional homologue of goosecoid in Drosophila". Development 122 (5): 1641–50. PMID 8625850.
  8. ↑ Yao J, Kessler DS (August 1, 2005). "Goosecoid promotes head organizer activity by direct repression of Xwnt8 in Spemann’s organizer". Development 128 (15): 2975–2987. PMID 11532920. Retrieved 14 April 2014.
  9. ↑ Yamada G, Mansouri A, Torres M, Stuart ET, Blum M, Schultz M, De Robertis EM, Gruss P (September 1995). "Targeted mutation of the murine goosecoid gene results in craniofacial defects and neonatal death". Development 121 (9): 2917–2922. PMID 7555718. Retrieved 14 April 2014.
  10. ↑ De Robertis, Eddy; Blum M; Niehrs C; Steinbeisser H (April 1992). "Mesoderm induction and origins of the embryonic axis: goosecoid and the organizer". Development 116: 167–171.
  11. ↑ Parry DA, Logan CV, Stegmann AP, Abdelhamed ZA, Calder A, Khan S, Bonthron DT, Clowes V, Sheridan E, Ghali N, Chudley AE, Dobbie A, Stumpel CT, Johnson CA (2013). "SAMS, a Syndrome of Short Stature, Auditory-Canal Atresia, Mandibular Hypoplasia, and Skeletal Abnormalities Is a Unique Neurocristopathy Caused by Mutations in Goosecoid". The American Journal of Human Genetics 93 (6): 1135–1142. doi:10.1016/j.ajhg.2013.10.027. PMC 3853132. PMID 24290375.
  12. ↑ Yamada G, Ueno K, Nakamura S, Hanamure Y, Yasui K, Uemura M, Eizuru Y, Mansouri A, Blum M, Sugimura K (April 1997). "Nasal and pharyngeal abnormalities caused by the mouse goosecoid gene mutation". Biochem Biophys Res Commun 233 (1): 161–165. doi:10.1006/bbrc.1997.6315. PMID 9144415. Retrieved 14 April 2014.
  13. ↑ Parry DA, Logan CV, Stegmann AP, Abdelhamed ZA, Calder A, Khan S, Bonthron DT, Clowes V, Sheridan E, Ghali N, Chudley AE, Dobbie A, Stumpel CT, Johnson CA (December 2013). "SAMS, a syndrome of short stature, auditory-canal atresia, mandibular hypoplasia, and skeletal abnormalities is a unique neurocristopathy caused by mutations in Goosecoid". Am J Hum Genet 93 (6): 1135–1142. doi:10.1016/j.ajhg.2013.10.027. PMC 3853132. PMID 24290375.
  14. ↑ Lemire EG, Hildes-Ripstein GE, Reed MH, Chudley AE (January 1998). "SAMS: provisionally unique multiple congenital anomalies syndrome consisting of short stature, auditory canal atresia, mandibular hypoplasia, and skeletal abnormalities.". Am J Med Genet 75 (3): 256–260. doi:10.1002/(sici)1096-8628(19980123)75:3<256::aid-ajmg5>3.0.co;2-o. PMID 9475592.

Further reading

  • Schlade-Bartusiak K, Macintyre G, Zunich J, Cox DW (2008). "A child with deletion (14)(q24.3q32.13) and auditory neuropathy". Am. J. Med. Genet. A 146 (1): 117–123. doi:10.1002/ajmg.a.32064. PMID 18074379. 
  • Hartwell KA, Muir B, Reinhardt F, Carpenter AE, Sgroi DC, Weinberg RA (2007). "The Spemann organizer gene, Goosecoid, promotes tumor metastasis". Proc. Natl. Acad. Sci. U.S.A. 103 (50): 18969–18974. doi:10.1073/pnas.0608636103. PMC 1748161. PMID 17142318. 
  • Barrios-Rodiles M, Brown KR, Ozdamar B, Bose R, Liu Z, Donovan RS, Shinjo F, Liu Y, Dembowy J, Taylor IW, Luga V, Przulj N, Robinson M, Suzuki H, Hayashizaki Y, Jurisica I, Wrana JL (2005). "High-throughput mapping of a dynamic signaling network in mammalian cells". Science 307 (5715): 1621–1625. doi:10.1126/science.1105776. PMID 15761153. 
  • Namciu SJ, Friedman RD, Marsden MD, Sarausad LM, Jasoni CL, Fournier RE (2004). "Sequence organization and matrix attachment regions of the human serine protease inhibitor gene cluster at 14q32.1". Mamm. Genome 15 (3): 162–178. doi:10.1007/s00335-003-2311-y. PMID 15014966. 
  • Foucher I, Montesinos ML, Volovitch M, Prochiantz A, Trembleau A (2003). "Joint regulation of the MAP1B promoter by HNF3beta/Foxa2 and Engrailed is the result of a highly conserved mechanism for direct interaction of homeoproteins and Fox transcription factors". Development 130 (9): 1867–1876. doi:10.1242/dev.00414. PMID 12642491. 
  • Danilov V, Blum M, Schweickert A, Campione M, Steinbeisser H (1998). "Negative autoregulation of the organizer-specific homeobox gene goosecoid". J. Biol. Chem. 273 (1): 627–635. doi:10.1074/jbc.273.1.627. PMID 9417125. 

External links

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