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First published online August 25, 2008
doi: 10.1242/10.1242/dev.021519


Development 135, 3081-3091 (2008)
Published by The Company of Biologists 2008


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Distinct sequential cell behaviours direct primitive endoderm formation in the mouse blastocyst

Berenika Plusa1,2,*,{ddagger}, Anna Piliszek1,*, Stephen Frankenberg1,3,*,{dagger}, Jérôme Artus1 and Anna-Katerina Hadjantonakis1,{ddagger}

1 Developmental Biology Program, Sloan-Kettering Institute, New York, USA.
2 Faculty of Life Sciences, Manchester University, Manchester, UK.
3 Department of Experimental Embryology, Institute of Genetics and Animal Breeding, Polish Academy of Sciences, Jastrzeebiec, Poland.

{ddagger} Authors for correspondence (e-mails: Berenika.Plusa{at}manchester.ac.uk;hadj{at}mskcc.org)

Accepted 24 July 2008

The first two lineages to differentiate from a pluripotent cell population during mammalian development are the extraembryonic trophectoderm (TE) and the primitive endoderm (PrE). Whereas the mechanisms of TE specification have been extensively studied, segregation of PrE and the pluripotent epiblast (EPI) has received comparatively little attention. A current model of PrE specification suggests PrE precursors exhibit an apparently random distribution within the inner cell mass of the early blastocyst and then segregate to their final position lining the cavity by the late blastocyst. We have identified platelet-derived growth factor receptor alpha (Pdgfr{alpha}) as an early-expressed protein that is also a marker of the later PrE lineage. By combining live imaging of embryos expressing a histone H2B-GFP fusion protein reporter under the control of Pdgfra regulatory elements with the analysis of lineage-specific markers, we investigated the events leading to PrE and EPI lineage segregation in the mouse, and correlated our findings using an embryo staging system based on total cell number. Before blastocyst formation, lineage-specific factors are expressed in an overlapping manner. Subsequently, a gradual progression towards a mutually exclusive expression of PrE- and EPI-specific markers occurs. Finally, cell sorting is achieved by a variety of cell behaviours and by selective apoptosis.

Key words: Lineage specification, Mouse blastocyst, ICM, Primitive endoderm, Epiblast, Pdgfr{alpha}, Histone H2B-GFP fusion, Live imaging


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Primitive endoderm finds its place

Development 2008 135: e1804. [Full Text]  






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