Alternative titles; symbols
HGNC Approved Gene Symbol: GSC2
Cytogenetic location: 22q11.21 Genomic coordinates (GRCh38): 22:19,146,993-19,150,292 (from NCBI)
Budarf et al. (1997) and Gottlieb et al. (1997) used multiple approaches to identify and characterize genes in a region of approximately 2 Mb that is deleted in most patients with DiGeorge syndrome (DGS; 188400) and velocardiofacial syndrome (VCFS; 192430). Database searches using the genomic sequence of the deleted region identified a functional gene with similarity to the homeodomain family of transcription factors. This novel gene, called goosecoid-like (GSCL), shares high homology with the goosecoid gene (GSC; 138890). The authors presented evidence that the gene is expressed in a limited number of adult tissues, as well as in early human development. The identification of GSCL required a genomic sequence-based approach because of its restricted expression and high GC content.
Using in situ hybridization, Gottlieb et al. (1998) found that the mouse Gscl gene was expressed in brain starting as early as embryonic day 9.5, and that expression continued in adults. The expression pattern was consistent with GSCL's having either an indirect role in the development of neural crest-derived structures or a direct role in a subset of the phenotype observed in DGS/VCFS, such as learning disorders or psychiatric disease.
Gong et al. (2003) described a large-scale screen to create an atlas of central nervous system (CNS) gene expression at the cellular level, and to provide a library of verified bacterial artificial chromosome (BAC) vectors and transgenic mouse lines offering experimental access to CNS regions, cell classes, and pathways. They found that Gscl was involved in neural specification. Inspection of BAC transgenic reporter lines at postnatal day 7 revealed robust expression in a subset of neuronal cell bodies within the interpeduncular nucleus (IPN). At embryonic day 15.5, Gscl expression in the developing IPN and in the ventricular zone adjacent to the developing IPN was evident, as were profiles of migrating neurons transiting from the ventricular zone to the area of the presumptive IPN. At embryonic day 10.5 only 2 cells expressed Gscl. These were present at the ventricular zone at the border of the developing mesencephalon and metencephalon, as expected from visualization of the expanding IPN progenitor pool in embryonic day 15.5 embryos.
Gottlieb et al. (1998) presented functional studies of the GSCL protein. They demonstrated that GSCL exhibited DNA sequence-specific recognition of sites bound by the Drosophila anterior morphogen, Bicoid. Several of these sites (TAATCCC) were found in the 5-prime upstream region of the GSCL gene itself, and Gottlieb et al. (1998) presented evidence suggesting that GSCL may regulate its own transcription.
Gross (2013) mapped the GSC2 gene to chromosome 22q11.21 based on an alignment of the GSC2 sequence (GenBank U96402) with the genomic sequence (GRCh37).
Funato et al. (2010) found that Gscl -/- mice had apparently normal neural architecture, with normal distribution of neurotransmitter immunoreactivity and normal afferent and efferent connections to and from the interpeduncular nucleus. However, Gscl -/- mice lacked expression of Dgcr14 (601755), which is located 2 kb downstream of Gscl in the same transcriptional direction, specifically in the interpeduncular nucleus. Gscl -/- mice showed abnormalities in rapid eye movement (REM) sleep, including reduced total time in REM sleep, fewer REM sleep episodes, reduced theta power during REM sleep, and increased arousability during REM sleep. Funato et al. (2010) concluded that the absence of Gscl and Dgcr14 in the interpeduncular nucleus results in altered regulation of REM sleep.
Budarf, M., Emanuel, B., Driscoll, D., Roe, B., Gottlieb, S. The DiGeorge syndrome minimal critical region contains a Goosecoid-like (GSCL) homeobox gene which is expressed early in human development. Medizinische Genetik 9: 19 only, 1997.
Funato, H., Sato, M., Sinton, C. M., Gautron, L., Williams, S. C., Skach, A., Elmquist, J. K., Skoultchi, A. I., Yanagisawa, M. Loss of Goosecoid-like and DiGeorge syndrome critical region 14 in interpeduncular nucleus results in altered regulation of rapid eye movement sleep. Proc. Nat. Acad. Sci. 107: 18155-18160, 2010. [PubMed: 20921407] [Full Text: https://doi.org/10.1073/pnas.1012764107]
Gong, S., Zheng, C., Doughty, M. L., Losos, K., Didkovsky, N., Schambra, U. B., Nowak, N. J., Joyner, A., Leblanc, G., Hatten, M. E., Heintz, N. A gene expression atlas of the central nervous system based on bacterial artificial chromosomes. Nature 425: 917-925, 2003. [PubMed: 14586460] [Full Text: https://doi.org/10.1038/nature02033]
Gottlieb, S., Emanuel, B. S., Driscoll, D. A., Sellinger, B., Wang, Z., Roe, B., Budarf, M. L. The DiGeorge syndrome minimal critical region contains a goosecoid-like (GSCL) homeobox gene that is expressed early in human development. Am. J. Hum. Genet. 60: 1194-1201, 1997. [PubMed: 9150167]
Gottlieb, S., Hanes, S. D., Golden, J. A., Oakey, R. J., Budarf, M. L. Goosecoid-like, a gene deleted in DiGeorge and velocardiofacial syndromes, recognizes DNA with a Bicoid-like specificity and is expressed in the developing mouse brain. Hum. Molec. Genet. 7: 1497-1505, 1998. [PubMed: 9700206] [Full Text: https://doi.org/10.1093/hmg/7.9.1497]
Gross, M. B. Personal Communication. Baltimore, Md. 5/20/2013.