Zebrafish serve as a valuable model organism for studying germ cell biology and reproductive processes.The AB strain of zebrafish is proposed to exhibit a polygenic sex determination system,where most males initially ...Zebrafish serve as a valuable model organism for studying germ cell biology and reproductive processes.The AB strain of zebrafish is proposed to exhibit a polygenic sex determination system,where most males initially develop juvenile ovaries before committing to male fate.In species with chromosomal sex determination,gonadal somatic cells are recognized as key determinants of germ cell fate.Notably,the loss of germ cells in zebrafish leads to masculinization,implying that germ cells harbor an intrinsic feminization signal.However,the specific signal triggering oogenesis in zebrafish remains unclear.In the present study,we identified foxl2l as an oocyte progenitor-specific gene essential for initiating oogenesis in germ cells.Results showed that foxl2l-knockout zebrafish bypassed the juvenile ovary stage and exclusively developed into fertile males.Further analysis revealed that loss of foxl2l hindered the initiation of oocyte-specific meiosis and prevented entry into oogenesis,leading to premature spermatogenesis during early gonadal development.Furthermore,while mutation of the pro-male gene dmrt1 led to fertile female differentiation,simultaneous disruption of foxl2l in dmrt1 mutants completely blocked oogenesis,with a large proportion of germ cells arrested as germline stem cells,highlighting the crucial role of foxl2l in oogenesis.Overall,this study highlights the unique function of foxl2l as a germ cell-intrinsic gatekeeper of oogenesis in zebrafish.展开更多
Extracellular membrane proteins are crucial for mediating cell attachment,recognition,and signal transduction in the testicular microenvironment,particularly germline stem cells.Cadherin 18(CDH18),a type Ⅱ classical ...Extracellular membrane proteins are crucial for mediating cell attachment,recognition,and signal transduction in the testicular microenvironment,particularly germline stem cells.Cadherin 18(CDH18),a type Ⅱ classical cadherin,is primarily expressed in the nervous and reproductive systems.Here,we investigated the expression of CDH18in neonatal porcine prospermatogonia(ProSGs)and murine spermatogonial stem cells(SSCs).Disruption of CDH18 expression did not adversely affect cell morphology,proliferation,self-renewal,or differentiation in cultured porcine ProSGs,but enhanced cell adhesion and prolonged cell maintenance.Transcriptomic analysis indicated that the down-regulation of CDH18 in ProSGs significantly up-regulated genes and signaling pathways associated with cell adhesion.To further elucidate the function of CDH18 in germ cells,Cdh18 knockout mice were generated,which exhibited normal testicular morphology,histology,andspermatogenesis.Transcriptomic analysis showed increased expression of genes associated with adhesion,consistent with the observations in porcine ProSGs.The interaction of CDH18withβ-catenin and JAK2 in both porcine ProSGs and murine SSCs suggested an inhibitory effect on the canonical Wnt and JAK-STAT signaling pathways during CDH18 deficiency.Collectively,these findings highlight the crucial role of CDH18 in regulating cell adhesion in porcine ProSGs and mouse SSCs.Understanding this regulatory mechanism provides significant insights into the testicular niche.展开更多
基金supported by the National Natural Science Foundation of China(32025037)Ministry of Science and Technology of China(2023YFD2401603)+2 种基金Ministry of Agriculture and Rural Affairs of China(NK2022010207)Science and Technology Special Fund of Hainan Province(ZDYF2024XDNY256)Natural Science Foundation of Wuhan。
文摘Zebrafish serve as a valuable model organism for studying germ cell biology and reproductive processes.The AB strain of zebrafish is proposed to exhibit a polygenic sex determination system,where most males initially develop juvenile ovaries before committing to male fate.In species with chromosomal sex determination,gonadal somatic cells are recognized as key determinants of germ cell fate.Notably,the loss of germ cells in zebrafish leads to masculinization,implying that germ cells harbor an intrinsic feminization signal.However,the specific signal triggering oogenesis in zebrafish remains unclear.In the present study,we identified foxl2l as an oocyte progenitor-specific gene essential for initiating oogenesis in germ cells.Results showed that foxl2l-knockout zebrafish bypassed the juvenile ovary stage and exclusively developed into fertile males.Further analysis revealed that loss of foxl2l hindered the initiation of oocyte-specific meiosis and prevented entry into oogenesis,leading to premature spermatogenesis during early gonadal development.Furthermore,while mutation of the pro-male gene dmrt1 led to fertile female differentiation,simultaneous disruption of foxl2l in dmrt1 mutants completely blocked oogenesis,with a large proportion of germ cells arrested as germline stem cells,highlighting the crucial role of foxl2l in oogenesis.Overall,this study highlights the unique function of foxl2l as a germ cell-intrinsic gatekeeper of oogenesis in zebrafish.
基金supported by the Jiangsu Seed Industry Revitalization Project(JBGS[2021]024)Fundamental Research Funds for the Central Universities(KYT2023002)+2 种基金Jiangsu Province Capability Improvement Project through Science,TechnologyEducation Jiangsu Provincial Medical Key Discipline(ZDXK202211)Shandong Province Natural Science Foundation(ZR2020MC074)
文摘Extracellular membrane proteins are crucial for mediating cell attachment,recognition,and signal transduction in the testicular microenvironment,particularly germline stem cells.Cadherin 18(CDH18),a type Ⅱ classical cadherin,is primarily expressed in the nervous and reproductive systems.Here,we investigated the expression of CDH18in neonatal porcine prospermatogonia(ProSGs)and murine spermatogonial stem cells(SSCs).Disruption of CDH18 expression did not adversely affect cell morphology,proliferation,self-renewal,or differentiation in cultured porcine ProSGs,but enhanced cell adhesion and prolonged cell maintenance.Transcriptomic analysis indicated that the down-regulation of CDH18 in ProSGs significantly up-regulated genes and signaling pathways associated with cell adhesion.To further elucidate the function of CDH18 in germ cells,Cdh18 knockout mice were generated,which exhibited normal testicular morphology,histology,andspermatogenesis.Transcriptomic analysis showed increased expression of genes associated with adhesion,consistent with the observations in porcine ProSGs.The interaction of CDH18withβ-catenin and JAK2 in both porcine ProSGs and murine SSCs suggested an inhibitory effect on the canonical Wnt and JAK-STAT signaling pathways during CDH18 deficiency.Collectively,these findings highlight the crucial role of CDH18 in regulating cell adhesion in porcine ProSGs and mouse SSCs.Understanding this regulatory mechanism provides significant insights into the testicular niche.
