Talking about sex

Male development is crucially dependent on the expression of a gene present on the Y cromosome

Published: Monday 15 December 1997

there is a genetic basis for sex determination in mammals -- females have two x chromosomes, whereas males have one x and one y chromosome. A gene known as Sry that is located on the y chromosome, is crucial for male sexual development. Mice with two x chromosomes can be developed as males if they are engineered to express the Sry gene. The gene is not the only factor to influence such changes. The x chromosome plays a more crucial role. Male development depends on a balance between Sry that promotes maleness and factors on the x chromosome that promote femaleness.

The duplication of a certain region of the x chromosome causes chromosomally male ( xy ) individuals to develop female sexual characteristics. Researchers say that the role of such duplications is mediated by a genetic locus known as dss (for dosage-sensitive sex reversal) that must be kept under check if Sry is to play its full role in male development.

A team of researchers led by R V Jamieson of the Children's Medical Research Institute, Went-worthville, Australia, has shown that at the earliest stages of male development in an xy individual, if Sry is to exert its full activity, dss has to be transiently suppressed. For suppressing dss activity, the developing male embryo inactivates the entire x chromosome -- a feat that is performed routinely by females.

In normal females, one of the two x chromosomes in each cell is permanently inactivated because of the expression of a special gene known as Xist. It suggests that when Xist is active, rest of the x chromosomes containing it remains inactive.

The researchers judged the state of activation of the x chromosome by monitoring the functioning of a foreign gene engineered in way so that it could be under control of a x chromosomal regulatory sequence. The foreign gene encoded a protein that gave rise to a blue colour after appropriate staining. If a cell was not coloured blue, the implication was that the regulatory sequence and by inference the chromosome as a whole, was inactive.

The activities of the Sry and Xist genes were assessed independently using genetic probes. Jamieson and his team found that even in male, the Xist gene remains active during the development of urogenital ridge -- a structure that mediates the formation of male germ cells.

The observations are based on experiments conducted on mice, but it is attractive to think of a similar activation of Xist (and therefore inactivation of the x chromosome, specifically of the dss locus) during male development in humans. It shows that the inactivation of x chromosome in males during a brief period, and in a relatively small population of cells, may be crucial for subsequent sexual development.

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