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4 - Regulation of X-chromosome inactivation in relation to lineage allocation in early mouse embryogenesis

Published online by Cambridge University Press:  07 August 2009

By
Neil Brockdorff
Edited by
Ashley Moffett ,
Charlie Loke  and
Anne McLaren
Neil Brockdorff
Affiliation:
MRC Clinical Sciences Centre, Imperial College Faculty of Medicine, UK
Ashley Moffett
Affiliation:
University of Cambridge
Charlie Loke
Affiliation:
University of Cambridge
Anne McLaren
Affiliation:
Cancer Research, UK
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Summary

Overview

The X-inactivation hypothesis, put forward by Mary Lyon in 1961, proposed that in mammals a single X chromosome is selected at random and genetically silenced early in embryogenesis. It was further proposed that the inactive state is stably maintained throughout the lifetime of the animal, and therefore that females are comprised of clonal cell populations derived from progenitor cells with either one X chromosome or the other inactive (Lyon 1961). In the intervening years the Lyon hypothesis has been verified on many levels and there has been significant progress towards understanding the molecular mechanisms governing this process (for a recent review see Heard et al. 1997). Along the way there have been a number of unanticipated surprises in the form of exceptions to the general pattern. Perhaps of most note is the finding that there is preferential inactivation of the paternally derived X chromosome (Xp), as opposed to random inactivation of either X chromosome, in marsupial mammals (Sharman 1971) and in extraembryonic lineages derived from the trophectoderm (TE) and primitive endoderm (PE) of early mouse embryos (Takagi & Sasaki 1975, Takagi et al. 1978).

The quest to understand how the paternally imprinted form of X inactivation is regulated has provided an important impetus that has aided our understanding of the earliest differentiative events in mammalian (eutherian) embryogenesis. Here I will focus on recent studies, which have led to a reappraisal of the classical model for initiation of imprinted X inactivation in mouse embryos.

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Biology and Pathology of Trophoblast , pp. 46 - 64
Publisher: Cambridge University Press
Print publication year: 2006

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References

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