XB-ART-55870Dev Genes Evol May 1, 2019; 229 (2-3): 53-72.
Transcriptome profiling reveals male- and female-specific gene expression pattern and novel gene candidates for the control of sex determination and gonad development in Xenopus laevis.
Xenopus laevis is an amphibian (frog) species widely used in developmental biology and genetics. To unravel the molecular machinery regulating sex differentiation of Xenopus gonads, we analyzed for the first time the transcriptome of developing amphibian gonads covering sex determination period. We applied microarray at four developmental stages: (i) NF50 (undifferentiated gonad during sex determination), (ii) NF53 (the onset of sexual differentiation of the gonads), (iii) NF56 (sexual differentiation of the gonads), and (iv) NF62 (developmental progression of differentiated gonads). Our analysis showed that during the NF50, the genetic female (ZW) gonads expressed more sex-specific genes than genetic male (ZZ) gonads, which suggests that a robust genetic program is realized during female sex determination in Xenopus. However, a contrasting expression pattern was observed at later stages (NF56 and NF62), when the ZW gonads expressed less sex-specific genes than ZZ gonads, i.e., more genes may be involved in further development of the male gonads (ZZ). We identified sexual dimorphism in the expression of several functional groups of genes, including signaling factors, proteases, protease inhibitors, transcription factors, extracellular matrix components, extracellular matrix enzymes, cell adhesion molecules, and epithelium-specific intermediate filaments. In addition, our analysis detected a sexually dimorphic expression of many uncharacterized genes of unknown function, which should be studied further to reveal their identity and if/how they regulate gonad development, sex determination, and sexual differentiation. Comparison between genes sex-specifically expressed in developing gonads of Xenopus and available transcriptome data from zebrafish, two reptile species, chicken, and mouse revealed significant differences in the genetic control of sex determination and gonad development. This shows that the genetic control of gonad development is evolutionarily malleable.
PubMed ID: 30972573
PMC ID: PMC6500517
Article link: Dev Genes Evol
Genes referenced: adam21 alb aldh3b1 alox12b anxa13 avil bcan birc5.1 cadm3 capn8 ccdc50 cdh26 cela1.1 chrd.1 cldn6.1 col1a1 col2a1 col3a1 col9a1 col9a3 crabp2 ctsh ctsk ctsl cx38 dcn ddx25 dhh dmrt2 dppa2 emx1 esr1 esr2 fbn3 fetub fgfbp1 fgfr4 foxa2 foxf1 foxh1 foxo1 foxr1 fzd10 fzd4 gata2 gde1 gdf1 gdf3 gja3 hoxa9 hoxd10 hoxd13 hrg hspb6 igf1 igf3 igfbp1 ihh isyna1 itga11 jak2 kdm6b klf15 klf9 kpna2 krt12.1 krt15.1 krt19 krt78.2 lhx1 lhx8 loc100145107 lum mafb matn2 matn4 mmp1 mmp11 mmp16 mmp2 mmp28 mmp7 mogat2.1 nes ngfr ocln ocm ocm.2 pabpn1l pcsk6 pou5f3.3 prss1 prss3 ptger3 ptx racgap1 rbm20 rbp2 rbp4 rdh16 rnf138 sag sdf2l1 serpina1 serpina3 serpinc1 serpinf2 serpini2 sh3glb2 shh smad4.1 sncg spdyc srpx2 sycp3 tfip11 timp2 timp3 twist1 vegt velo1 vill vtn vwa2 wnt10b wnt11 wnt11b wnt3a wnt7b wnt8b zar1 zp2 zp3 zp4 zpd zpy1
GO keywords: sex determination
Article Images: [+] show captions
|Fig. 1. Structural changes in developing gonads. a, b At stage NF50, there is no difference in the gonad structure between genetic sexes (ZW and ZZ). Such undifferentiated gonads (arrows) are composed of the somatic cells of coelomic epithelium (ce) covering the gonad, and germ cells (g) located inside; the germ cells are attached to the coelomic epithelium. The somatic cells gather in the gonad center forming gonadal medulla (m). At stage NF53, the first sexual differences appear in the gonad structure; in the differentiating ovaries (c, ZW), the germ cells remain in the peripheral position forming the ovarian cortex, whereas the centrally located medulla remains sterile. In the ZZ (male) gonads at the onset of sexual differentiation (d, the onset of the testis differentiation), the germ cells (g) detach from the coelomic epithelium and move towards the gonad center (medulla, m). At stage NF56, the differentiating ovaries (e) becomes compartmentalized into cortex and medulla; all germ cells (g) are located in the cortex and are attached to the coelomic epithelium; an ovarian cavity forms in the medulla (asterisk). In the differentiating testes (f), the germ cells (g) are dispersed and the cortex and medulla are absent. At stage NF62, the ovaries (g) contain large ovarian cavity (asterisk); the ovarian cortex contains meiotic cells (o). In the testes (h), the germ cells (g) are located within the testis cords (encircled). Scale bar, 25 μm|
|Fig. 2 Diagram of changes in the number of genes upregulated and downregulated (≥ 2-fold change) between different stages in ZW gonads (a) and ZZ gonads (b)|
|Fig. 3. Diagram of changes in the number of genes with higher expression in ZW or ZZ gonads (≥ 2-fold change).|
|Fig. 4. Subcellular distribution of gene products (obtained from the Ingenuity Pathway Analysis).|