Cellular mechanisms important in the development of the human central nervous system include differentiation, cell migration and homeostatic apoptosis. Epithelial fusion is particularly important and abnormalities are linked to a number of CNS diseases associated with failure of embryonic fissure closure. My research group is focused on understanding the molecular control mechanisms important in epithelial fusion in the developing CNS. Our model system is optic fissure closure in the eye, in animal models such as the zebrafish.
Epithelial fusion defects in the eye are relatively common, examples are ocular coloboma (0.5:10,000) and anophthalmia/microphthalmia (2.1:10,000). In addition to studies in zebrafish, we have built a database of coloboma families and patients. With this database, to date we have identified two new genes causing ocular coloboma: ZFHX1B& FADD.
Moosajee M, Gregory-Evans K, Ellis C, Seabra MC, Gregory-Evans CY. Translational bypass of nonsense mutations in rep1, pax2.1 and lamb1 highlights a viable therapeutic option for untreatable genetic eye disease. Hum Mol Genet. 2008;17:3987-4000.
Gregory-Evans CY, Moosajee M, Hodges MD, Mackay DS, Game L, Vargesson N, Bloch-Zupan A, Ruschendorf F, Santos-Pinto L, Wackens G, Gregory-Evans K. SNP genome scanning localises oto-dental syndrome to chromosome 11q13 and microdeletions at this locus implicate FGF3 in dental and inner ear disease and FADD in ocular coloboma. Hum Mol Genet. 2007;16:2482-93.
Gregory-Evans CY; Vieira H; Dalton R; Adams GG; Salt A; Gregory-Evans K. Ocular coloboma and high myopia with Hirschsprung disease associated with a novel ZFHX1B missense mutation and trisomy 21. Am J Med Genet A. 2004;131:86-90.
Hodges MD, Bibb LC, Gregory-Evans K and Gregory-Evans CY. Characterisation of the genomic and transcriptional structure of the CRX gene: substantial differences between the human and mouse genes. Genomics 2002;80: 531-542.
Bibb LC, Holt JKL, Tarttelin EE, Hodges MD, Gregory-Evans K, Lucas RJ, Sowden JC and Gregory-Evans CY. Temporal and spatial expression patterns of the CRX gene and its downstream targets. Critical differences during human and mouse eye development. Hum Mol Genet 2001;10:1571-1579.
Freund CL, Gregory-Evans CY, Furukawa T, Papaioannou M, Looser J, Ploder L, Bellingham J, Ng D, Herbrick J-AS, Duncan A, Scherer SW, Tsui L-C, Loutradis-Anagnostou A, Cepko CL, Jacobson SG, Bhattacharya SS, and McInnes RR. Cone-rod dystrophy due to mutations in a novel photoreceptor-specific homeobox gene (CRX) required for maintenance of the mammalian photoreceptor. Cell1997;91:543-553.