Figure 2. The process of X-inactivation. (a) Xist RNA switched off during passage through the germline. (b) Both X-chromosomes active in early cleavage-stage embryo. Stable, accumulated Xist signal associated with paternal X (Xp). (c) By midstage blastocyst, Xp inactive and associated with stable Xist signal in extraembryonic lineages (trophectoderm), maternal X (Xm) active. Unstable Xist RNA visible as punctate dot from both Xist alleles in cells of the inner cell mass (ICM). Both X-chromosomes active. (d) At day 5.5 of development, embryo implants and cells of embryo proper begin to differentiate. Random X-inactivation initiated – most cells now show unstable Xist transcript from Xa and stable, accumulating transcript from Xi. (e) By day 8.5, Xi associated with stable, accumulated Xist transcript, unstable Xist RNA from Xa switched off. Xi inactive and Xa active throughout adult life.