Sequential X chromosome inactivation coupled with cellular differentiation in early mouse embryos
Abstract
Only one of the two X chromosomes is active in each somatic cell of adult female eutherian mammals, making the females (XX) equivalent to the males (XY) with respect to X chromosome dosage1-4. Biochemical analyses showing that both X chromosomes are active in female mouse embryos in midcleavage stage4-8 indicate that X chromosome differentiation involves inactivation. This event occurs in most or all cells of the embryo at the blastocyst stage4,7-9, when there are two cell types, the outer sphere of trophectoderm cells and the inner cell mass (ICM). Because there is genetic evidence that both X chromosomes are potentially active in ICM cells10, it has been suggested that X chromosome inactivation has occurred in only the trophectoderm cells9. Further, one of us (M.M.)4 has proposed that X chromosome differentiation is linked to cellular differentiation, occurring at different times in different cell populations as they `depart' or terminally differentiate from a pluripotent fetal `stem line' (Fig. 1). Analysis of a large number of inner cell masses isolated immunosurgically from female blastocysts has yielded data consistent with the presence of two active X chromosomes11, but ICMs are so small that the biochemical assay used was at the limit of its accuracy. (Nevertheless, a computer analysis of the data8 indicated two ICM populations differing twofold with respect to X chromosome activity.) More tissue is available for analysis in post-implantation embryos, in which, on the above hypothesis, we would expect two active X chromosomes in the pluripotent epiblast region before gastrulation, but only one in the corresponding extra-embryonic ectoderm (a trophectoderm-derived tissue12) and primary endoderm (ICM-derived12, see Fig. 1). We report here that this is the case; we also show that inactivation is complete in the epiblast (fetal precursor) cells between 6.0 and 6.5 d of gestation at the onset of gastrulation.
- Publication:
-
Nature
- Pub Date:
- September 1979
- DOI:
- 10.1038/281311a0
- Bibcode:
- 1979Natur.281..311M