Germline stem cells are critical for sexual fate decision of germ cells

Abstract

Egg or sperm? The mechanism of sexual fate decision in germ cells has been a long‐standing issue in biology. A recent analysis identified foxl3 as a gene that determines the sexual fate decision of germ cells in the teleost fish, medaka. foxl3/Foxl3 acts in female germline stem cells to repress commitment into male fate (spermatogenesis), indicating that the presence of mitotic germ cells in the female is critical for continuous sexual fate decision of germ cells in medaka gonads. Interestingly, foxl3 is found in most vertebrate genomes except for mammals. This provides the interesting possibility that the sexual fate of germ cells in mammals is determined in a different way compared to foxl3‐possessing vertebrates. Considering the fact that germline stem cells are the cells where foxl3 begins to express and sexual fate decision initiates and mammalian ovary does not have typical germline stem cells, the mechanism in mammals may have been co‐evolved with germline stem cell loss in mammalian ovary.

Comparison of sex determination mechanism of germ cells between birds and fish: Cloning and expression analyses of chicken forkhead box L3‐like gene

“…Additionally, the timing of chicken foxl3-like gene expression differed from that of medaka foxl3, which is expressed in both male and female germ cells at the same developmental stage. 7,8 In male medaka, FOXL3 levels were downregulated in surrounding testicular somatic cells, thereby displaying temporal expression and inducing spermatogenesis. By contrast, we did not observe up-regulation of chicken foxl3-like gene expression in the male gonad.…”

“…7,8 Additionally, FOXL3 levels in germline stem cells is down-regulated by spermatogenesis induced by testicular somatic cells, and functional sperm cells have been observed in the ovaries of foxl3 −/− female medaka. In medaka (Oryzias latipes), foxl3/FOXL3 is expressed in both male and female germline stem cells and associated with sperm-egg fate decision.…”

“…In medaka (Oryzias latipes), foxl3/FOXL3 is expressed in both male and female germline stem cells and associated with sperm-egg fate decision. 7,8 Additionally, FOXL3 levels in germline stem cells is down-regulated by spermatogenesis induced by testicular somatic cells, and functional sperm cells have been observed in the ovaries of foxl3 −/− female medaka. The foxl3 gene is conserved in all vertebrates, except amphibians and placental mammals, [9][10][11] but absent in mice (Mus musculus), in which the mechanism of deciding germ-cell fate differs from that of medaka.…”

A compromised gsdf signaling leads to gamatogenesis confusion and subfertility in medaka

“…Although sex determining system is highly diverse in vertebrates, it is common that the primordial germ cells (PGCs) reach the gonads in female to undergo cell proliferation and oogenesis, in contrast to the retaining of mitotically quiescent state for a while before the initiation of spermatogenesis in male gonads. Indifferent germ cells require instructive signal(s) from the surrounding somatic cells to enter their sexual path, in other words, the initiation of oogenesis and spermatogenesis controlled by the somatic cells steps by steps(Tanaka, 2016). Genetic manipulation of germ cell foxl3 gene ( forkhead -domain gene 3 as an intrinsic determiner of sperm–egg fate) or the germ cell numbers in medaka disrupt the communication between germ cells and surrounding somatic cells, and subsequently result in ovotestis development(Tanaka, 2016).…”

“…Indifferent germ cells require instructive signal(s) from the surrounding somatic cells to enter their sexual path, in other words, the initiation of oogenesis and spermatogenesis controlled by the somatic cells steps by steps(Tanaka, 2016). Genetic manipulation of germ cell foxl3 gene ( forkhead -domain gene 3 as an intrinsic determiner of sperm–egg fate) or the germ cell numbers in medaka disrupt the communication between germ cells and surrounding somatic cells, and subsequently result in ovotestis development(Tanaka, 2016). foxl3 expression was merely changed among the adult testes of normal XY males, transgenic XX males and Sissy intersexes (own data unpublished), suggesting a rare alteration of germ stem cells under the gsdf signals influence.…”