Fig. 3 Sex change involves transition from female- to male-specific expression and gene neofunctionalization. Sex change involves transition from female-

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Fig. 3 Sex change involves transition from female- to male-specific expression and gene neofunctionalization. Sex change involves transition from female- to male-specific expression and gene neofunctionalization. (A) Mammalian model of sex determination and development. In males, SRY (sex-determining region Y) activates SOX9 (SRY-related HMG box 9) to initiate male development while blocking expression of feminization genes that would, in turn, antagonize masculinizing expression (9). (B) Teleost model of sexual development. Diverse factors determine sex in fishes, yet conserved downstream effectors act in feminizing and masculinizing pathways to promote female or male development, respectively, while antagonizing the opposing sexual pathway. Testosterone is a prohormone and is converted to estrogen (E2) by gonadal aromatase (encoded by cyp19a1a) to promote ovarian function or to 11-KT by the products of hsd11b2 and cyp11c1 to promote testicular function. (C) Normalized expression of classical sex-pathway genes across sex change in bluehead wrasse gonads. At stage 2, cyp19a1a is sharply down-regulated, after which feminizing expression collapses as female fish transition to males. Up-regulation of masculinizing gene expression begins with amh and its receptor amhr2. Classically feminizing genes within the R-spondin/Wnt/β-catenin signaling pathway (wnt4a/b, rspo1, and two transcripts annotated as fstl4 are shown as examples), and also foxl2, are duplicated in the bluehead wrasse with orthologs showing testis-specific expression. Erica V. Todd et al. Sci Adv 2019;5:eaaw7006 Copyright © 2019 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).