Professor Anne Ferguson-Smith & Dr Mitsuteru Ito. Department of Genetics.
Rtl1/Peg11 is a eutherian-specific imprinted retrotransposon-derived gene required for normal placentation. The gene is expressed in the endothelial cells of the fetal capillaries of the placenta and knockout results in placental capillary defects, prenatal growth retardation and neonatal lethality (Sekita et al., 2008; Ito et al., 2015). HowRtl1 regulates normal placentation is not known.
During angiogenesis, the degradation of the basement membrane and extracellular matrix (ECM) promotes formation of new capillaries (Jain, 2003). In hepatocarcinogenesis, previous work has shown that Rtl1 cleaves ECM components resulting in release of growth factors (Riordan et al., 2013). With this in mind, we propose that, in normal placentation, Rtl1 promotes cleavage of the basement membrane and ECM to promote the vascularisation of the fetal capillaries. This PhD project will test this hypothesis and explore the function of this remarkable gene in placenta development.
Sekita, Y. et al. (2008). Nat. Genet. 40, 243–248
Ito, M. et al. (2015). Development 142, 2425-30
Jain, R. K. (2003). Nat Med. 9, 685-693
Riordan, J. D. et al. (2013). PLoS Genet. 9, e1003441
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