Pantelis Georgiades
Embryology/Developmental Genetics and Stem Cell Lab
Department of Biological Sciences,
University of Cyprus
Research:
Our lab carries out research to understand clinically important and fundamental, but still unexplained, phenomena of embryonic development using mouse conceptuses (embryo/foetus + extraembryonic tissues) and mouse embryo-derived stem cells. In particular, we are interested in elucidating the cellular and genetic basis of:
(a) Extraembryonic tissue development with emphasis on placenta development using mutant mouse conceptuses and genetically manipulated trophoblast stem (TS) cells.
(b) Interactions between the conceptus and the mother (trophoblast-uterus interactions) important for mediating embryo growth and viability and maternal well-being.
(c) Influences of extraembryonic tissues on early embryo development. The emphasis here is on the role of trophoblast in fundamental aspects of early embryonic patterning such as primitive streak formation and gastrulation. Experiments for this include the use of Ets2 gene knockout mouse embryos.
(d) Early embryonic patterning and organogenesis, with emphasis on primitive streak inititation and gastrulation events.
We are also interested in developing new methodologies for manipulating genes in vivo and in stem cells in a cell-type-specific manner.
The long-term goals of our research include:
(a) Understanding and developing therapies for the most common, but as yet incurable diseases of pregnancy (pregnancy complications such as first trimester miscarriages, intrauterine growth retardation and preeclampsia).
(b) Understanding organ formation in the context of early embryogenesis and stem cell biology in order to provide new therapies for a variety of incurable diseases through organ/tissue generation/regeneration (regenerative medicine).
We employ cutting-edge methodologies such as Molecular Biology techniques, embryo culture and micro-surgery, embryo-derived stem cell establishment/culture, lentivirus-mediated genetic manipulation (gene overexpression and gene knockdown via RNAi) of embryos and embryo-derived stem cells, RNA in situ hybridization, immunohistochemistry, histology and the use of transgenic/knockout mice.
Research team:
Christoforos Odiatis
Christiana Polydorou
Stavros Nicolaou
Katerina Drakou
Fotini Charalambous
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1. Mouse embryos at different embryonic stages from the blastocyst stage (far-left image) to the foetal stage (far-right image). Note the transformation of the initially amorphous and organ-less epiblast into a foetus.
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2. In vivo trophoblast-specific lentivirus-mediated GFP expression (green colour). A, preimplantation (E3.75) mouse conceptus. B, E5.5 postimplantation mouse conceptus. C,D E16.5 placenta and fetus, respectively. Note the absence of GFP expresson in the embryo and foetus, but not the trophoblast. ICM, inner cell mass. Epc, ectoplacental cone trophoblast. Exe, extraembryonic ectoderm trophoblast. Emb, embryo.
3. Wild-type (left photo) and Ets2 mutant (right photo) mouse embryos at the early primitive streak stage, showing expression of the primitive streak marker gene T (left photo). Note the absence of primitive streak formation in Ets2 mutant embryos. Arrowhead indicates the embryonic-extraembryonic junction.
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4. Trophoblast-uterus interactions: Adjacent sections of the decidua basalis of an E18.5 mouse placenta showing a part of a central maternal spiral artery (cma) and the p57Kip2-positive invasive interstitial trophoblast (trophoblast glycogen cells).
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5. Cultured trophoblast stem (TS) cells transduced with a Green fluorescent protein (GFP)-expressing Lentivirus (left panel: bright field view; right panel: fluorescent view).
Selected Publications:
-- Odiatis C,
Georgiades P (2010) New insights for Ets2 function in trophoblast using lentivirus-mediated gene knockdown in trophoblast stem cells. Placenta 31, 630-640.
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Georgiades P, Cox B, Gertsenstein M, Chawengsaksophak K, Rossant J (2007) Trophoblast-specific gene manipulation using lentivirus-based vectors. BioTechniques 42:317-325.
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Georgiades P and Rossant J (2006) Ets2 is necessary in trophoblast for normal embryonic anteroposterior axis development. Development 133, 1059-1068.
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Georgiades P (2004) The possible clinical relevance of mouse placental research. SICC (Invited expert section), 17-12-2004.
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Georgiades P, Ferguson-Smith AC, Burton GJ (2002) Comparative developmental anatomy of murine and human definitive placentae. Placenta 23, 3-19.
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Georgiades P, Ogilvy S, Duval H, Licence DR, Charnock-Jones DS, Smith SK, Print CG (2002) VavCre transgenic mice: a tool for mutagenesis in hematopoietic and endothelial lineages. Genesis 34, 251-6.
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Georgiades P, Watkins M, Burton GJ, Ferguson-Smith AC (2001) Roles for genomic imprinting and the zygotic genome in placental development. Proceedings of the National Academy of Sciences USA 98, 4522-4527.
-- Ferguson-Smith AC, Tevendale M,
Georgiades P, Grandjean (2001) Balanced translocations for the analysis of imprinted regions of the mouse genome. Methods in Molecular Biology 181, 41-54.
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Georgiades P, Watkins M, Surani MA, Ferguson-Smith AC (2000) Parental origin-specific developmental defects in mice with uniparental disomy for chromosome 12. Development 127, 4719-28.
-- Takada S, Tevendale M, Baker J,
Georgiades P, Campbell E, Freeman T, Johnson MH, Paulsen M, Ferguson-Smith AC (2000) Delta-like and gtl2 are reciprocally expressed, differentially methylated linked imprinted genes on mouse chromosome 12. Current Biology 10, 1135-8.
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Georgiades P, Chierakul C,Ferguson-Smith AC (1998)Parental origin effects in human trisomy for chromosome14q: implications for genomic imprinting.Journal of Medical Genetics35, 821 824.