Laboratory of Developmental Biology
Group of Reproductive Biology

ProfessorMinoru Tanaka
Sex Determination/Differentiation and its Related Reproductive Phenomena
Assistant ProfessorMariko Kikuchi
Sex Determination of Germ Cells
▶Laboratory HP
Minoru Tanaka Professor
Lab members

Reproduction is an essential process in all animals to give rise to the next generation. It has been attracting much attention due to a variety of fascinating reproductive phenomena. However, many mechanisms underlying these phenomena remain unknown. Our lab welcomes students/postdoctoral candidates eager to explore and address these issues.

The Core Mechanism of Sex Determination, Differentiation, and Reversal

Our recent studies have demonstrated the presence of a core mechanism that ensures the development of either female or male sex. In other words, sex determination is compared to a kind of seesaw balanced between females and males; failure to develop into males allows cells and/or tissues to become females, and any obstacle to female development causes cells and/or tissues to develop into males. We have been demonstrating that sex is maintained as an unbalanced status between female and male. Therefore, elucidating the core mechanism involved in this process is essential for understanding sex determination/differentiation, and mechanism of sex reversal.

Reproductive Phenomena Linked to the Core Mechanism of Sex

Our lab has demonstrated that germ-line stem cells constitute one of the major components of the core mechanism. In addition, the core mechanism is associated with regulation of gonadal size, fecundity, and the initiation of spermatogenesis at the onset of puberty. We are now exploring this field to understand these uncovered phenomena stemming from the core mechanism.


Core mechanism of sex
The sex of medaka is genetically determined (the sex determination gene on the Y chromosome determines male fate). Medaka does not exhibit sex reversal during normal development. However, if the number of germ cells during development is less or none, medaka display female to male sex reversal (left image), whereas an excessive number of germ cells causes male to female sex reversal. This indicates that germ cells are essential for ovarian (female) development and that somatic cells are predisposed to male development. This process is independent of presence or absence of the sex determination gene.


Core mechanism during normal development
During normal development, expression of the sex determination gene enhances the ability of somatic cells to masculinize germ cells, whereas in the absence of the sex determination gene, germ cells override the intrinsic ability of somatic cells to become male and thus feminize the body.


Core mechanism regulates reproductive phenomena.
The core mechanism is closely associated with many other reproductive phenomena. It regulates sex reversal (anemone fish), size of gonads (fecundity: many eggs in sunfish), and initiation of spermatogenesis (medaka), and constitutes the molecular source that evolutionally generates a variety of sex determination systems (mouse: XY/XX, Xenopus: ZW/ZZ, lizard: temperature).


  1. Kikuchi et al, (2020) foxl3, a sexual switch in germ cells, initiates two independent molecular pathways for commitment to oogenesis in medaka. Proc. Natl. Acad. Sci. USA (2020) 117, 12174-12181.
  2. Sakae et al, (2020) Starvation causes female-to-male sex reversal through lipid metabolism in the teleost fish, medaka (Oryzias latipes). Biology Open (2020) 9, bio050054.
  3. Nishimura et al, Germ cells in the teleost fish medaka have an inherent feminizing effect. PLoS Genetics (2018) 14(3) e1007259
  4. Nishimura, et al., (2015) foxl3 is a germ cell-intrinsic factor involved in sperm-egg fate decision in medaka.Science 349, 328-331.
  5. Nishimura, et al., (2014) Analysis of a novel gene, Sdgc, reveals sex chromosome-dependent differences of medaka germ cells prior to gonad formation.Development 141, 3363-3369.

  6. Nakamura, et al., (2012) Hyperproliferation of mitotically active germ cells dues todefective anti-Müllerian hormone signaling mediates sex reversal in medaka. Development 139, 2283-2287.

  7. Nakamura, et al., (2010) Identification of germline stem cells in the ovary of the teleost medaka. Science 328, 1561-1563.

  8. Kurokawa, et al., (2007) Germ cells are essential for sexual dimorphism in the medaka gonad. Proc. Natl. Acad. Sci. USA 104, 16958-16963.

  9. Morinaga, C., et al., (2007) The hotei mutation of medaka in the anti-Mullerian hormone receptor causes the dysregulation of germ cell and sexual development. Proc. Natl. Acad. Sci. USA 104, 9691-9696.

  10. Nishimura, T. and Tanaka, M. The mechanism of germline sex determination in vertebrates. Biol. Reprod. (2016) In press. (Invited Review)

  11. Tanaka, M. (2013) Vertebrate female germline – the acquisition of femaleness. WIREs Dev. Biol. doi: 10.1002/wdev.131. (Invited Review)