The Questions of Developmental Biology

chromatin that remains condensed throughout most
of the cell cycle and replicates later than most of the
other chromatin (the euchromatin) of the nucleus.
The heterochromatic (inactive) X chromosome can
often be seen on the nuclear envelope of female cells
and is referred to as a Barr body (Figure 5.22; Barr
and Bertram 1949). X chromosome inactivation must
occur early in development. Using a mutated X
chromosome that would not inactivate, Tagaki and Abe (1990) showed that the expression of two
X chromosomes per cell in mouse embryos leads to ectodermal cell death and the absence of
mesoderm formation, eventually causing embryonic death at day 10 of gestation.
The early inactivation of one X chromosome per cell has important
phenotypic consequences. One of the earliest analyses of X chromosome
inactivation was performed by Mary Lyon (1961), who observed coat
color patterns in mice. If a mouse is heterozygous for an autosomal gene
controlling hair pigmentation, then it resembles one of its two parents, or
has a color intermediate between the two. In either case, the mouse is a
single color. But if a female mouse is heterozygous for a pigmentation
gene on the X chromosome, a different result is seen: patches of one
parental color alternate with patches of the other parental color (Figure
5.23).
Lyon proposed the following hypothesis to account for these results:
1. Very early in the development of female mammals, both X chromosomes are active.
2. As development proceeds, one X chromosome is turned off in each cell.
3. This inactivation is random. In some cells, the paternally derived X chromosome is inactivated;
in other cells, the maternally derived X chromosome is shut off.
4. This process is irreversible. Once an X chromosome has been inactivated, the same X
chromosome is inactivated in all that cell's progeny. Since X inactivation happens relatively early
in development, an entire region of cells derived from a single cell may all have the same X
chromosome inactivated. Thus, all tissues in female mammals are mosaics of two cell types.
The Lyon hypothesis of X chromosome inactivation provides an excellent account of
differential gene inactivation at the level of transcription. Some interesting exceptions to the
general rules further show its importance. First, X chromosome inactivation holds true only for