The Mechanism of Germline Sex Determination in Vertebrates

Abstract

Germ cells are the common cells of origin for the two different types of gametes, sperm and eggs. In vertebrates so far examined, the sex of germ cells is determined by gonadal somatic cells. However, influenced by the somatic cells, how germ cells adopt their sexual fates by intrinsic factors has long been unclear in vertebrates. We recently identified forkhead box L3 (FOXL3) as a germ cell-intrinsic factor involved in the sperm-egg fate decision in the teleost fish medaka (Oryzias latipes). On the basis of the results obtained by the analysis of foxl3/FOXL3 expression and loss-of-function mutants, we review when and how germ cell sex is regulated non-cell-autonomously and cell-autonomously. We then discuss the fact that the germline sex determination pathway is genetically distinct from other essential gametogenic pathways such as meiotic entry and the establishment of germline stem cells. Another extraordinary finding in the foxl3 mutant is that functional sperm can be produced in the ovary, which provides a new notion that gametogenesis can proceed regardless of the sex of the surrounding somatic cells once the sexual identity of germ cells is established in medaka.

Foxl2 and Its Relatives Are Evolutionary Conserved Players in Gonadal Sex Differentiation

“…On the other hand adult foxl3 -/-XY gonads developed as morphologically and functionally normal testes, indicating that foxl3 is dispensable for male gonadal development and maintenance. Together, these findings indicate that Foxl3 is a germline-intrinsic factor involved in sperm-egg fate decision [Nishimura et al, 2015;Nishimura and Tanaka, 2016].…”

Transcriptomic analysis of the differentiating ovary of the protogynous ricefield eel Monopterus albus

“…Foxl3 , an ancient duplicated copy of foxl2 , has been shown to be present in teleosts, reptiles, birds, and marsupials [ 44 ]. In medaka, adult XX fish with disrupted foxl3 developed functional sperms in the expanded germinal epithelium of a histologically functional ovary [ 45 ], and foxl3 is considered to be a sex-switching gene that suppresses the initiation of spermatogenesis [ 46 ]. In other teleosts like Atlantic salmon and European sea bass, in contrast, foxl3 transcripts were predominantly expressed in the testis compared to ovaries, and possibly involved in testis physiology [ 47 ].…”

Flexible adaptation of male germ cells from female iPSCs of endangered Tokudaia osimensis

“…This finding raises the possibility that the genetic contributors to germ cell sex are equal in both sexes of this species. Some teleosts show high sexual plasticity in the determination of their germ cell sex ( 11 , 12 ). However, it is unrealistic to use the embryos, gonads, and germ cells to elucidate the sex determination mechanism of this endangered species.…”