title: Harvesting clues from genome wide transcriptome analysis for exploring thalidomide mediated anomalies in eye development of chick embryo: Nitric oxide rectifies the thalidomide mediated anomalies by swinging back the system to normal transcriptome pattern.
abstract: Thalidomide, the notorious teratogen is known to cause various developmental abnormalities, among which a range of eye deformations are very common. From the clinical point of view, it is necessary to pinpoint the mechanisms of teratogens that tune the gene expression. However, to our knowledge, the molecular basis of eye deformities under thalidomide treatmenthas not been reported so far. Present study focuses on the possible mechanism by which thalidomide affects eye development and the role of Nitric Oxide in recovering thalidomide-mediated anomalies of eye development using chick embryo and zebrafish models with transcriptome analysis. Transcriptome analysis showed that 403 genes were up-regulated and 223 genes were down-regulated significantly in thalidomide pre-treated embryos. 8% of the significantly modulated genes have been implicated in eye development including Pax6, OTX2, Dkk1 and Shh. A wide range of biological process and molecular function was affected by thalidomide exposure. Biological Processes including structural constituent of eye lens and Molecular functions such as visual perception and retinal metabolic process formed strong annotation clustersindicating the adverse effects of thalidomide on eye development and function. Here, we have discussed the whole embryo transcriptome with the expression of PAX6, SOX2, and CRYAAgenes from developing eyes. Our experimental data showing structural and functional aspects includingeye size, lens transparency and optic nerve activity and bioinformatics analyses of transcriptome suggest that NO could partially protect thalidomide treated embryos from its devastating effects on eye development and function.
authors.affiliation: Vascular Biology Lab, AU-KBC Research Centre, Chennai, Tamil Nadu, India.
authors.forename: Pavitra
authors.initials: P
authors.lastname: Kumar
authors.affiliation: Vascular Biology Lab, AU-KBC Research Centre, Chennai, Tamil Nadu, India; Department of Biotechnology, Anna University, Chennai, Tamil Nadu, India.
authors.forename: Dharanibalan
authors.initials: D
authors.lastname: Kasiviswanathan
authors.affiliation: Vascular Biology Lab, AU-KBC Research Centre, Chennai, Tamil Nadu, India; Department of Biotechnology, Anna University, Chennai, Tamil Nadu, India.
authors.forename: Lakshmikirupa
authors.initials: L
authors.lastname: Sundaresan
authors.affiliation: Ion Channel Biology Lab, AU-KBC Research Centre, Chennai, Tamil Nadu, India.
authors.forename: Priyadarshan
authors.initials: P
authors.lastname: Kathirvel
authors.affiliation: Vascular Biology Lab, AU-KBC Research Centre, Chennai, Tamil Nadu, India.
authors.forename: Vimal
authors.initials: V
authors.lastname: Veeriah
authors.affiliation: Department of Biotechnology, Anna University, Chennai, Tamil Nadu, India.
authors.forename: Priya
authors.initials: P
authors.lastname: Dutta
authors.affiliation: Ion Channel Biology Lab, AU-KBC Research Centre, Chennai, Tamil Nadu, India.
authors.forename: Kavitha
authors.initials: K
authors.lastname: Sankaranarayanan
authors.affiliation: SciGenom Labs, Cochin, Kerala, India.
authors.forename: Ravi
authors.initials: R
authors.lastname: Gupta
authors.affiliation: Vascular Biology Lab, AU-KBC Research Centre, Chennai, Tamil Nadu, India; Department of Biotechnology, Anna University, Chennai, Tamil Nadu, India. Electronic address: soovro@yahoo.ca.
authors.forename: Suvro
authors.initials: S
authors.lastname: Chatterjee
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D002642:Chick Embryo; D002645:Chickens; D005123:Eye / Q000187:drug effects / Q000196:embryology; D005124:Eye Abnormalities / Q000139:chemically induced* / Q000201:enzymology; D020869:Gene Expression Profiling; D009569:Nitric Oxide / Q000378:metabolism*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D013792:Thalidomide; D059467:Transcriptome / Q000187:drug effects / Q000235:genetics*; D015027:Zebrafish
chemical_list: D020030:Nitric Oxide Donors; D009569:Nitric Oxide; D013792:Thalidomide
keywords: Chick embryo; Eye development; Nitric oxide; Teratogenicity; Thalidomide; Transcriptome