Zfy gene expression patterns are not compatible with a primary role in mouse sex determination

Abstract

The Y chromosome determines maleness in mammals. A Y chromosome-linked gene diverts the indifferent embryonic gonad from the default ovarian pathway in favour of testis differentiation, initiating male development. Study of this basic developmental switch requires the isolation of the testis-determining gene, termed TDF in humans and Tdy in mice. ZFY, a candidate gene for TDF, potentially encodes a zinc-finger protein, and has two Y-linked homologues, Zfy-1 and Zfy-2, in mice. Although ZFY, Zfy-1 and Zfy-2 seem to map to the sex-determining regions of the human and mouse Y chromosomes, there is no direct evidence that these genes are involved in testis determination. We report here that Zfy-1 but not Zfy-2 is expressed in differentiating embryonic mouse testes. Neither gene, however, is expressed in We/We mutant embryonic testes which lack germ cells. These observations exclude both Zfy-1 and Zfy-2 as candidates for the mouse testis-determining gene.

Evidence for multiple functional copies of the male sex-determining locus, sry, in African murine rodents

“…Zfy is present in two copies in Mus musculus (Mardon et al 1989;Nagamine et al 1989) and has amplified up to 26 times on the Y chromosome in other rodents Lau et al 1992;Nagamine 1994). The two Mus musculus Zfy copies are expressed in the testis and do not appear to be functionally redundant (Koopman et al 1989). …”

How Australian mammals contributed to our understanding of sex determination and sex chromosomes

“…Our conclusion that ZFY was the wrong gene was soon confirmed independently by the finding (by another young Australian, Peter Koopman, a postdoc in Robin Lovell-Badge's London laboratory), that ZFY was expressed in the germ cells of the mouse testis, but not in the somatic cells (Koopman et al 1989), where the sex determination signal had to be received.…”

Zfy1 encodes a nuclear sequence‐specific DNA binding protein

“…Although previously thought to have a function in testis determination, such a role has now been excluded [1][2][3]. It has been suggested that the Z f y l gene may have a function in spermatogenesis, perhaps as a transcription factor [4].…”

“…Although a primary role in sex determination has now been ruled out [2,3] the conservation of this gene on the Y chromosome of placental mammals suggests it has some important male-specific function, perhaps in spermatogenesis [4]. A gene closely related to ZFY, called ZFX, is also present on the X chromosome of all placental mammals so far analysed [4].…”