X‐chromosome Inactivation and Developmental Patterns in Mammals

Abstract

Summary 1. The review considers information from mammalian embryology relevant to X‐chromosome inactivation, and from X‐inactivation relevant to mammalian embryology. 2. Properties of the inactive‐X, by which it may be recognized are: sex chromatin, heteropycnosis, late replication and the absence of gene product. Each of these has advantages and disadvantages in particular circumstances. In some species the X carries constitutive heterochromatin, which must be distinguished from the facultative region. 3. The time of X‐chromosome inactivation can be estimated from the time of appearance of sex chromatin or late replication, or inferred from the appearance of heterozygotes for X‐linked genes or of experimental chimaeras. The estimated time varies with species, and in the mouse and rabbit is near the time of increase in RNA synthesis. 4. Whereas in eutherian mammals either the maternally or the paternally derived X may be inactivated in different cell lines, in marsupials the paternal X is always the inactive one. 5. During development various factors act to distort the patterns produced by random X‐inactivation. These factors include cell selection, transfer of gene product, and migration and mingling of cells. 6. There is no clear evidence that X‐chromosome inactivation is not complete. 7. In female germ cells both X‐chromosomes appear to be active. In male ones both X and Y appear inactive during most of spermatogenesis, although probably in early stages all X chromosomes present are active. 8. The active and inactive X‐chromosomes may be differentiated by presence or absence of some non‐histone protein or other polyanionic substance. 9. If the genes concerned in synthesis or attachment of this substance are on the X‐chromosome then the differentiation will be self‐maintaining. 10. The initiation of the differentiation requires either the attachment of different X‐chromosomes to different sites, or some interaction of X‐linked and autosomal genes, concerned in inducing or repressing activity. Some possible models are discussed.

Absence of dosage compensation for a sex-linked enzyme in butterflies (Heliconius)

“…This difference in gene dosage is "compensated" in mammals and in Drosophila, so that males and females produce equal amounts of enzymes from such sex-linked genes. In male Drosophila compensation is achieved by transcription of X-linked genes at twice the female rate (Lucchesi, 1973); in mammals, one of the X-chromosomes in every somatic cell of the female is inactivated, so that females have the same effective gene dose as males (Lyon, 1972). Neither of these mechanisms has been demonstrated to occur in other organisms.…”

Cell Lineage Analysis during Liver Development Using the spfash-Heterozygous Mouse

“…Such analysis in rodent livers suggests that hepatocytes randomly allocate their progeny in liver development and regeneration (Iannaccone et al, 1987;Khokha et al, 1994;Ng and Iannaccone, 1992). We have immunohistochemically demonstrated that, in spf ash (sparse-fur with abnormal skin and hair)-heterozygous mouse liver (DeMars et al, 1976;Hodges and Rosenberg, 1989;Ohtake et al, 1987), ornithine transcarbamylase (OTC) expression is mosaic in hepatocytes because of the random inactivation of either the X chromosome carrying the spf ash gene or the wild-type gene (Lyon, 1961(Lyon, , 1972Wareham and Williams, 1986), and that the mosaic pattern can be analyzed in both two and three dimensions (Shiojiri et al, 1997). Analysis of the OTC mosaic pattern in the fetal mouse liver, where biliary cell differentiation occurs, may be helpful in resolving the issues mentioned above.…”

Dosage compensation of the sex-linked enzyme phosphoglucomutase in the orthoptera

“…In mammals, dosage compensation is achieved by inactivation of one of the X-chromosomes in the somatic cells of the female (the homogametic sex), so equalising the gene dose in males and females (Lyon, 1972). In Drosophila, an alternative mechanism of dosage compensation (dosage compensation sensu strictu) has evolved, whereby the effective dose of X-linked genes is equalised in the two sexes by an increased rate of transcription in the male (Lucchesi, 1973).…”