Foxl3, a Sexual Switch in Germ Cells, Initiates Two Independent Molecular Pathways for Commitment to Oogenesis in Medaka

Total Page:16

File Type:pdf, Size:1020Kb

Foxl3, a Sexual Switch in Germ Cells, Initiates Two Independent Molecular Pathways for Commitment to Oogenesis in Medaka foxl3, a sexual switch in germ cells, initiates two independent molecular pathways for commitment to oogenesis in medaka Mariko Kikuchia, Toshiya Nishimuraa,1, Satoshi Ishishitab, Yoichi Matsudab,c, and Minoru Tanakaa,2 aDivision of Biological Science, Graduate School of Science, Nagoya University, 464-8602 Nagoya, Japan; bAvian Bioscience Research Center, Graduate School of Bioagricultural Sciences, Nagoya University, 464-8601 Nagoya, Japan; and cDepartment of Animal Sciences, Graduate School of Bioagricultural Sciences, Nagoya University, 464-8601 Nagoya, Japan Edited by John J. Eppig, The Jackson Laboratory, Bar Harbor, ME, and approved April 8, 2020 (received for review October 23, 2019) Germ cells have the ability to differentiate into eggs and sperm and elegans (8–10). To date, however, neither protein has been im- must determine their sexual fate. In vertebrates, the mechanism of plicated in germline feminization. commitment to oogenesis following the sexual fate decision in During oogenesis in mice, several transcription factors facili- germ cells remains unknown. Forkhead-box protein L3 (foxl3)isa tate folliculogenesis: lhx8 (LIM homeobox 8) and figla (factor in switch gene involved in the germline sexual fate decision in the the germline alpha) regulate differentiation of primordial follicles teleost fish medaka (Oryzias latipes). Here, we show that foxl3 or- (11–14), and nobox (newborn ovary homeobox), which acts ganizes two independent pathways of oogenesis regulated by REC8 downstream of Lhx8, is indispensable for the formation of sec- meiotic recombination protein a (rec8a), a cohesin component, and ondary follicles (12, 15). It remains unknown how these tran- F-box protein (FBP)47(fbxo47), a subunit of E3 ubiquitin ligase. In scription factors cooperate after sexually indifferent germ cells mutants of either gene, germ cells failed to undergo oogenesis but commit to oogenesis. developed normally into sperm in testes. Disruption of rec8a Here, we show that foxl3 orchestrates two independent path- resulted in arrest at a meiotic pachytenelike stage specifically in ways for oogenesis: one leading to meiosis by rec8a and the other females, revealing a sexual difference in meiotic progression. to follicle development by fbxo47. In addition, we show that the Analyses of fbxo47 mutants showed that this gene regulates tran- fbxo47-downstream pathway ensures that germ cells do not de- DEVELOPMENTAL BIOLOGY scription factors that facilitate folliculogenesis: LIM homeobox 8 viate from the oogenesis pathway during early meiotic prophase α (lhx8b), factor in the germline (figla), and newborn ovary ho- I; otherwise, the sexual fate of the germ cells would change to meobox (nobox). Interestingly, we found that the fbxo47 pathway spermatogenesis. Thus, we propose that the diplotene stage of ensures that germ cells do not deviate from an oogenic pathway meiotic prophase I is the point of no return for establishing until they reach diplotene stage. The mutant phenotypes together germline feminization. with the timing of their expression imply that germline feminiza- tion is established during early meiotic prophase I. Results rec8a Is Required for Female Meiotic Progression. To investigate the germline sex determination | foxl3 | rec8a | fbxo47 | oogenesis function of rec8a in germline feminization, we generated rec8a commitment Significance erm cells, which have the potential to differentiate into eggs and sperm, must determine their sexual fate. In the teleost G In teleost fish, unlike mammals, retinoic acid (RA) does not exert fish medaka (Oryzias latipes), the onset of the germline sexual a conspicuous feminization effect of germ cells. Instead, in the fate decision is triggered by foxl3 (forkhead box protein L3) (1). teleost fish medaka, foxl3 serves as a germ cell-autonomous During medaka gonadal development, foxl3 expression is main- factor acting at the very beginning of the sexual fate decision. tained only in female germ cells, and the loss-of-function mutant This study shows that foxl3 initiates oogenesis through two of foxl3 results in production of functional sperm in the ovary, genetically independent pathways, meiosis and follicular devel- indicating that foxl3 is required for suppression of spermatogenesis opment. One pathway, involving rec8a, drives female-specific in female germ cells (1). However, the specific role of foxl3 in regulation of meiosis. The other, involving fbxo47, both directs germline feminization (process of commitment to oogenesis) has follicular development and suppresses spermatogenesis com- not been clarified. mitment. The involvement of two evolutionarily conserved fac- To elucidate the molecular pathways organized by foxl3,we tors in oogenesis suggests the existence of an RA-independent previously identified rec8a (REC8 meiotic recombination protein pathway that promotes oogenesis, common in vertebrates. In a) and fbxo47 (F-box protein 47) as direct targets of FOXL3 (2). addition, our findings reveal the timing of the establishment of rec8a and fbxo47 transcripts are detected in mitotic germ cells − − germ cell feminization. expressing foxl3 in wild-type ovaries but not in foxl3 / ovaries and are indicated to act downstream of foxl3 during germline sex Author contributions: M.K. and M.T. designed research; M.K., T.N., and S.I. performed determination (2). rec8a is one of two Rec8 orthologs resulting research; T.N. contributed new reagents/analytic tools; M.K., S.I., Y.M., and M.T. analyzed from the teleost-specific whole-genome duplication (3). REC8 is data; and M.K. and M.T. wrote the paper. a meiosis-specific kleisin subunit of the cohesin complex, which The authors declare no competing interest. plays crucial roles in various meiosis-associated chromosomal This article is a PNAS Direct Submission. events, including chromosomal axis formation and homolog as- Published under the PNAS license. sociation (4). Rec8-null mutant mice of both sexes are sterile and 1Present address: Division of Marine Life Science, Graduate School of Fisheries Sciences, fail to complete meiotic prophase I (5, 6). On the other hand, the Hokkaido University, 041-8611 Hakodate, Japan. F-box domain-containing protein FBXO47 has been implicated 2To whom correspondence may be addressed. Email: [email protected]. to act as a subunit of Skp1-cullin1-FBP (SCF)-type E3 ubiquitin This article contains supporting information online at https://www.pnas.org/lookup/suppl/ ligases (7). Notably, germ cells in the fbxo47 mutant exhibit de- doi:10.1073/pnas.1918556117/-/DCSupplemental. fects in meiotic recombination in both mice and Caenorhabditis www.pnas.org/cgi/doi/10.1073/pnas.1918556117 PNAS Latest Articles | 1of8 Downloaded by guest on September 23, 2021 − − mutants by CRISPR/Cas9 (SI Appendix, Fig. S1). rec8a / XY fbxo47 mutants was similar to that observed in wild-type sper- males developed normal testes with mature sperm (SI Appendix, matogenesis (Fig. 2 C, Bottom, and SI Appendix, Fig. S4H). Fig. S2 A and B). Although the hatching rate of eggs fertilized To test the hypothesis that fbxo47-mutant germ cells committed − − with rec8a / XY sperm was slightly lower than that of eggs with to spermatogenesis, we examined the expression of shippo1b,a − − wild-type sperm, rec8a / XY sperm were fertile (SI Appendix, spermatocyte and spermatid marker, by in situ hybridization. The − − Fig. S2 C and D). On the other hand, rec8a / XX females were shippo1b signal was detected in both the control wild-type XY sterile, and all of the mutant ovaries lacked follicles (Fig. 1 A and testes and the fbxo47-mutant XX ovaries (Fig. 2 D and E). − − B). Because we could not find germ cells at the diplotene stage in Interestingly, shippo1b was already expressed in fbxo47 / XX the mutant ovaries, meiosis was likely arrested before the dip- gonads at 15 days posthatching (dph), consistent with the time − − lotene stage (Fig. 1 A and B, Insets). when spermatogenesis initiated in the foxl3 / XX gonads (1) We next examined the synaptonemal complex (SC) formation (Fig. 2 F and G and SI Appendix,Fig.S5). −/− +/− in rec8a ovaries. In the control (rec8a ) ovaries, synapsis To further analyze the function of fbxo47, we introduced a marker SYCP1 (a central element of SC) localized between ho- bacterial artificial chromosome (BAC) containing the fbxo47 mologous chromosomes of zygotene to pachytene oocytes, and allele with enhanced green fluorescent protein (EGFP) into foxl3 these signals disappeared in diplotene oocytes (Fig. 1 C–E). In mutants (SI Appendix, Fig. S6 and Table S3). None of the EGFP- −/− − − rec8a ovaries, although SYCP1 localized normally to the forming expressing germ cells in foxl3 / XX gonads (n = 5) exhibited SC axes of zygotene chromosomes, the signal became punctate at a spermatogenic progression (Fig. 2 H and I). Collectively, these pachytenelike stage (Fig. 1 F–H). These results suggest that SC axes −/− data strongly suggest that fbxo47 is a downstream factor of foxl3 prematurely disassembled in the rec8a oocytes and that rec8a is that is essential for suppressing spermatogenesis. required for the stability of the SC axis during the pachytene stage. To explore the possibility that abnormal oocytes were eliminated Two Pathways Downstream of foxl3 Contribute to Germline by apoptosis, we immunostained for activated caspase-3 (cleaved Feminization. As described above, two foxl3-downstream genes −/− caspase-3 [CC-3]) in wild-type and rec8a ovaries. We first mea- rec8a and fbxo47 are female-specific regulators of meiosis pro-
Recommended publications
  • Screening and Identification of Key Biomarkers in Clear Cell Renal Cell Carcinoma Based on Bioinformatics Analysis
    bioRxiv preprint doi: https://doi.org/10.1101/2020.12.21.423889; this version posted December 23, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. Screening and identification of key biomarkers in clear cell renal cell carcinoma based on bioinformatics analysis Basavaraj Vastrad1, Chanabasayya Vastrad*2 , Iranna Kotturshetti 1. Department of Biochemistry, Basaveshwar College of Pharmacy, Gadag, Karnataka 582103, India. 2. Biostatistics and Bioinformatics, Chanabasava Nilaya, Bharthinagar, Dharwad 580001, Karanataka, India. 3. Department of Ayurveda, Rajiv Gandhi Education Society`s Ayurvedic Medical College, Ron, Karnataka 562209, India. * Chanabasayya Vastrad [email protected] Ph: +919480073398 Chanabasava Nilaya, Bharthinagar, Dharwad 580001 , Karanataka, India bioRxiv preprint doi: https://doi.org/10.1101/2020.12.21.423889; this version posted December 23, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. Abstract Clear cell renal cell carcinoma (ccRCC) is one of the most common types of malignancy of the urinary system. The pathogenesis and effective diagnosis of ccRCC have become popular topics for research in the previous decade. In the current study, an integrated bioinformatics analysis was performed to identify core genes associated in ccRCC. An expression dataset (GSE105261) was downloaded from the Gene Expression Omnibus database, and included 26 ccRCC and 9 normal kideny samples. Assessment of the microarray dataset led to the recognition of differentially expressed genes (DEGs), which was subsequently used for pathway and gene ontology (GO) enrichment analysis.
    [Show full text]
  • Ovarian Gene Expression in the Absence of FIGLA, an Oocyte
    BMC Developmental Biology BioMed Central Research article Open Access Ovarian gene expression in the absence of FIGLA, an oocyte-specific transcription factor Saurabh Joshi*1, Holly Davies1, Lauren Porter Sims2, Shawn E Levy2 and Jurrien Dean1 Address: 1Laboratory of Cellular and Developmental Biology, NIDDK, National Institutes of Health, Bethesda, MD 20892, USA and 2Department of Biomedical Informatics, Vanderbilt University Medical Center, Nashville, TN 37232, USA Email: Saurabh Joshi* - [email protected]; Holly Davies - [email protected]; Lauren Porter Sims - [email protected]; Shawn E Levy - [email protected]; Jurrien Dean - [email protected] * Corresponding author Published: 13 June 2007 Received: 11 December 2006 Accepted: 13 June 2007 BMC Developmental Biology 2007, 7:67 doi:10.1186/1471-213X-7-67 This article is available from: http://www.biomedcentral.com/1471-213X/7/67 © 2007 Joshi et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Abstract Background: Ovarian folliculogenesis in mammals is a complex process involving interactions between germ and somatic cells. Carefully orchestrated expression of transcription factors, cell adhesion molecules and growth factors are required for success. We have identified a germ-cell specific, basic helix-loop-helix transcription factor, FIGLA (Factor In the GermLine, Alpha) and demonstrated its involvement in two independent developmental processes: formation of the primordial follicle and coordinate expression of zona pellucida genes. Results: Taking advantage of Figla null mouse lines, we have used a combined approach of microarray and Serial Analysis of Gene Expression (SAGE) to identify potential downstream target genes.
    [Show full text]
  • Table S1 the Four Gene Sets Derived from Gene Expression Profiles of Escs and Differentiated Cells
    Table S1 The four gene sets derived from gene expression profiles of ESCs and differentiated cells Uniform High Uniform Low ES Up ES Down EntrezID GeneSymbol EntrezID GeneSymbol EntrezID GeneSymbol EntrezID GeneSymbol 269261 Rpl12 11354 Abpa 68239 Krt42 15132 Hbb-bh1 67891 Rpl4 11537 Cfd 26380 Esrrb 15126 Hba-x 55949 Eef1b2 11698 Ambn 73703 Dppa2 15111 Hand2 18148 Npm1 11730 Ang3 67374 Jam2 65255 Asb4 67427 Rps20 11731 Ang2 22702 Zfp42 17292 Mesp1 15481 Hspa8 11807 Apoa2 58865 Tdh 19737 Rgs5 100041686 LOC100041686 11814 Apoc3 26388 Ifi202b 225518 Prdm6 11983 Atpif1 11945 Atp4b 11614 Nr0b1 20378 Frzb 19241 Tmsb4x 12007 Azgp1 76815 Calcoco2 12767 Cxcr4 20116 Rps8 12044 Bcl2a1a 219132 D14Ertd668e 103889 Hoxb2 20103 Rps5 12047 Bcl2a1d 381411 Gm1967 17701 Msx1 14694 Gnb2l1 12049 Bcl2l10 20899 Stra8 23796 Aplnr 19941 Rpl26 12096 Bglap1 78625 1700061G19Rik 12627 Cfc1 12070 Ngfrap1 12097 Bglap2 21816 Tgm1 12622 Cer1 19989 Rpl7 12267 C3ar1 67405 Nts 21385 Tbx2 19896 Rpl10a 12279 C9 435337 EG435337 56720 Tdo2 20044 Rps14 12391 Cav3 545913 Zscan4d 16869 Lhx1 19175 Psmb6 12409 Cbr2 244448 Triml1 22253 Unc5c 22627 Ywhae 12477 Ctla4 69134 2200001I15Rik 14174 Fgf3 19951 Rpl32 12523 Cd84 66065 Hsd17b14 16542 Kdr 66152 1110020P15Rik 12524 Cd86 81879 Tcfcp2l1 15122 Hba-a1 66489 Rpl35 12640 Cga 17907 Mylpf 15414 Hoxb6 15519 Hsp90aa1 12642 Ch25h 26424 Nr5a2 210530 Leprel1 66483 Rpl36al 12655 Chi3l3 83560 Tex14 12338 Capn6 27370 Rps26 12796 Camp 17450 Morc1 20671 Sox17 66576 Uqcrh 12869 Cox8b 79455 Pdcl2 20613 Snai1 22154 Tubb5 12959 Cryba4 231821 Centa1 17897
    [Show full text]
  • Transcription Factors SOHLH1 and SOHLH2 Coordinate Oocyte Differentiation Without Affecting Meiosis I
    Transcription factors SOHLH1 and SOHLH2 coordinate oocyte differentiation without affecting meiosis I Yong-Hyun Shin, … , Vasil Mico, Aleksandar Rajkovic J Clin Invest. 2017;127(6):2106-2117. https://doi.org/10.1172/JCI90281. Research Article Development Reproductive biology Following migration of primordial germ cells to the genital ridge, oogonia undergo several rounds of mitotic division and enter meiosis at approximately E13.5. Most oocytes arrest in the dictyate (diplotene) stage of meiosis circa E18.5. The genes necessary to drive oocyte differentiation in parallel with meiosis are unknown. Here, we have investigated whether expression of spermatogenesis and oogenesis bHLH transcription factor 1 (Sohlh1) and Sohlh2 coordinates oocyte differentiation within the embryonic ovary. We found that SOHLH2 protein was expressed in the mouse germline as early as E12.5 and preceded SOHLH1 protein expression, which occurred circa E15.5. SOHLH1 protein appearance at E15.5 correlated with SOHLH2 translocation from the cytoplasm into the nucleus and was dependent on SOHLH1 expression. NOBOX oogenesis homeobox (NOBOX) and LIM homeobox protein 8 (LHX8), two important regulators of postnatal oogenesis, were coexpressed with SOHLH1. Single deficiency of Sohlh1 or Sohlh2 disrupted the expression of LHX8 and NOBOX in the embryonic gonad without affecting meiosis. Sohlh1-KO infertility was rescued by conditional expression of the Sohlh1 transgene after the onset of meiosis. However, Sohlh1 or Sohlh2 transgene expression could not rescue Sohlh2-KO infertility due to a lack of Sohlh1 or Sohlh2 expression in rescued mice. Our results indicate that Sohlh1 and Sohlh2 are essential regulators of oocyte differentiation but do not affect meiosis I.
    [Show full text]
  • Supplementary Materials
    Supplementary materials Supplementary Table S1: MGNC compound library Ingredien Molecule Caco- Mol ID MW AlogP OB (%) BBB DL FASA- HL t Name Name 2 shengdi MOL012254 campesterol 400.8 7.63 37.58 1.34 0.98 0.7 0.21 20.2 shengdi MOL000519 coniferin 314.4 3.16 31.11 0.42 -0.2 0.3 0.27 74.6 beta- shengdi MOL000359 414.8 8.08 36.91 1.32 0.99 0.8 0.23 20.2 sitosterol pachymic shengdi MOL000289 528.9 6.54 33.63 0.1 -0.6 0.8 0 9.27 acid Poricoic acid shengdi MOL000291 484.7 5.64 30.52 -0.08 -0.9 0.8 0 8.67 B Chrysanthem shengdi MOL004492 585 8.24 38.72 0.51 -1 0.6 0.3 17.5 axanthin 20- shengdi MOL011455 Hexadecano 418.6 1.91 32.7 -0.24 -0.4 0.7 0.29 104 ylingenol huanglian MOL001454 berberine 336.4 3.45 36.86 1.24 0.57 0.8 0.19 6.57 huanglian MOL013352 Obacunone 454.6 2.68 43.29 0.01 -0.4 0.8 0.31 -13 huanglian MOL002894 berberrubine 322.4 3.2 35.74 1.07 0.17 0.7 0.24 6.46 huanglian MOL002897 epiberberine 336.4 3.45 43.09 1.17 0.4 0.8 0.19 6.1 huanglian MOL002903 (R)-Canadine 339.4 3.4 55.37 1.04 0.57 0.8 0.2 6.41 huanglian MOL002904 Berlambine 351.4 2.49 36.68 0.97 0.17 0.8 0.28 7.33 Corchorosid huanglian MOL002907 404.6 1.34 105 -0.91 -1.3 0.8 0.29 6.68 e A_qt Magnogrand huanglian MOL000622 266.4 1.18 63.71 0.02 -0.2 0.2 0.3 3.17 iolide huanglian MOL000762 Palmidin A 510.5 4.52 35.36 -0.38 -1.5 0.7 0.39 33.2 huanglian MOL000785 palmatine 352.4 3.65 64.6 1.33 0.37 0.7 0.13 2.25 huanglian MOL000098 quercetin 302.3 1.5 46.43 0.05 -0.8 0.3 0.38 14.4 huanglian MOL001458 coptisine 320.3 3.25 30.67 1.21 0.32 0.9 0.26 9.33 huanglian MOL002668 Worenine
    [Show full text]
  • TCF3 Antibody Product Type: Primary Antibodies Description: Rabbit Polyclonal to TCF3 Immunogen:3 Synthetic Peptides (Human) Conjugated to KLH
    PRODUCT INFORMATION Product name: TCF3 antibody Product type: Primary antibodies Description: Rabbit polyclonal to TCF3 Immunogen:3 synthetic peptides (human) conjugated to KLH. Reacts with: Hu, Ms Tested applications: ELISA and WB. GENE INFORMATION Gene Symbol: TCF3 Gene Name: transcription factor 3 (E2A immunoglobulin enhancer binding factors E12/E47) Ensembl ID: ENSG00000071564 Entrez GeneID:6929 GenBank Accession number: M65214.1 Omim ID:147141 Swiss­Prot:P15923 Molecular weight of TCF3: 67.6kDa (Isoform E12) and 67.265kDa (Isoform E47) Function: Heterodimers between TCF3 and tissue­specific basic helix­loop­helix (bHLH) proteins play major roles in determining tissue­specific cell fate during embryogenesis, like muscle or early B­cell differentiation. Dimers bind DNA on E­box motifs: 5'­CANNTG­3'. Binds to the kappa­E2 site in the kappa immunoglobulin gene enhancer. Subunit structure: Efficient DNA binding requires dimerization with another bHLH protein. Forms a heterodimer with ASH1 and TWIST2. Isoform E12 interacts with GRIPE and FIGLA By similarity. Interacts with PTF1A and TGFB1I1. Component of a nuclear TAL­1 complex composed at least of CBFA2T3, LDB1, TAL1 and TCF3 By similarity. Interacts with UBE2I. Subcellular localization: Nucleus Involvement in disease:Chromosomal aberrations involving TCF3 are cause of forms of pre­B­cell acute lymphoblastic leukemia (B­ALL). Translocation t(1;19)(q23;p13.3) with PBX1; Translocation t(17;19)(q22;p13.3) with HLF. Inversion inv(19)(p13;q13) with TFPT. APPLICATION NOTE Recommended dilution: • ELISA: Antibody specificity was verified by direct ELISA against the 3 immunogen peptides. A titer of 1/15000 has been determined. Appropriate specificity controls were run.
    [Show full text]
  • Dynamic Transcriptional and Chromatin Accessibility Landscape of Medaka Embryogenesis
    Downloaded from genome.cshlp.org on October 8, 2021 - Published by Cold Spring Harbor Laboratory Press Dynamic Transcriptional and Chromatin Accessibility Landscape of Medaka Embryogenesis Yingshu Li1,2,3,+, Yongjie Liu1,2,3,+, Hang Yang1,2,3, Ting Zhang1,2, Kiyoshi Naruse4,*, Qiang Tu1,2,3,* 1 State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Innovation Academy for Seed Design, Chinese Academy of Sciences, Beijing 100101, China 2 Key Laboratory of Genetic Network Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China 3 University of Chinese Academy of Sciences, Beijing 100049, China 4 Laboratory of Bioresources, National Institute for Basic Biology, Okazaki 444-8585, Aichi, Japan + These authors are joint first authors and contributed equally to this work. * Corresponding authors: [email protected], [email protected] Abstract Medaka (Oryzias latipes) has become an important vertebrate model widely used in genetics, developmental biology, environmental sciences, and many other fields. A high-quality genome sequence and a variety of genetic tools are available for this model organism. However, existing genome annotation is still rudimentary, as it was mainly based on computational prediction and short-read RNA-seq data. Here we report a dynamic transcriptome landscape of medaka embryogenesis profiled by long-read RNA-seq, short-read RNA-seq, and ATAC-seq. Integrating these datasets, we constructed a much-improved gene model set including about 17,000 novel isoforms, identified 1600 transcription factors, 1100 long non-coding RNAs, and 150,000 potential cis-regulatory elements as well. Time-series datasets provided another dimension of information.
    [Show full text]
  • Supplementary Table 1
    Supplementary Table 1. 492 genes are unique to 0 h post-heat timepoint. The name, p-value, fold change, location and family of each gene are indicated. Genes were filtered for an absolute value log2 ration 1.5 and a significance value of p ≤ 0.05. Symbol p-value Log Gene Name Location Family Ratio ABCA13 1.87E-02 3.292 ATP-binding cassette, sub-family unknown transporter A (ABC1), member 13 ABCB1 1.93E-02 −1.819 ATP-binding cassette, sub-family Plasma transporter B (MDR/TAP), member 1 Membrane ABCC3 2.83E-02 2.016 ATP-binding cassette, sub-family Plasma transporter C (CFTR/MRP), member 3 Membrane ABHD6 7.79E-03 −2.717 abhydrolase domain containing 6 Cytoplasm enzyme ACAT1 4.10E-02 3.009 acetyl-CoA acetyltransferase 1 Cytoplasm enzyme ACBD4 2.66E-03 1.722 acyl-CoA binding domain unknown other containing 4 ACSL5 1.86E-02 −2.876 acyl-CoA synthetase long-chain Cytoplasm enzyme family member 5 ADAM23 3.33E-02 −3.008 ADAM metallopeptidase domain Plasma peptidase 23 Membrane ADAM29 5.58E-03 3.463 ADAM metallopeptidase domain Plasma peptidase 29 Membrane ADAMTS17 2.67E-04 3.051 ADAM metallopeptidase with Extracellular other thrombospondin type 1 motif, 17 Space ADCYAP1R1 1.20E-02 1.848 adenylate cyclase activating Plasma G-protein polypeptide 1 (pituitary) receptor Membrane coupled type I receptor ADH6 (includes 4.02E-02 −1.845 alcohol dehydrogenase 6 (class Cytoplasm enzyme EG:130) V) AHSA2 1.54E-04 −1.6 AHA1, activator of heat shock unknown other 90kDa protein ATPase homolog 2 (yeast) AK5 3.32E-02 1.658 adenylate kinase 5 Cytoplasm kinase AK7
    [Show full text]
  • TBP2 Is Essential for Germ Cell Development by Regulating Transcription and Chromatin Condensation in the Oocyte
    Downloaded from genesdev.cshlp.org on September 24, 2021 - Published by Cold Spring Harbor Laboratory Press TBP2 is essential for germ cell development by regulating transcription and chromatin condensation in the oocyte Emese Gazdag,1,4 Ange`le Santenard,1,2,4 Ce´line Ziegler-Birling,1,2 Gioia Altobelli,1,3 Olivier Poch,3 La`szlo` Tora,1,5 and Maria-Elena Torres-Padilla1,2,6 1Department of Functional Genomics, Institut de Ge´ne´tique et de Biologie Mole´culaire et Cellulaire (IGBMC), UMR 7104 CNRS, UdS, INSERM U964, BP 10142, F-67404 Illkirch Cedex, CU de Strasbourg, France; 2Department of Developmental and Cell Biology, Institut de Ge´ne´tique et de Biologie Mole´culaire et Cellulaire (IGBMC), UMR 7104 CNRS, UdS, INSERM U964, BP 10142, F-67404 Illkirch Cedex, CU de Strasbourg, France; 3Bioinformatics and Integrative Biology Laboratory, Institut de Ge´ne´tique et de Biologie Mole´culaire et Cellulaire (IGBMC), UMR 7104 CNRS, UdS, INSERM U964, BP 10142, F-67404 Illkirch Cedex, CU de Strasbourg, France Development of the germline requires consecutive differentiation events. Regulation of these has been associated with germ cell-specific and pluripotency-associated transcription factors, but the role of general transcription factors (GTFs) remains elusive. TATA-binding protein (TBP) is a GTF involved in transcription by all RNA polymerases. During ovarian folliculogenesis in mice the vertebrate-specific member of the TBP family, TBP2/ TRF3, is expressed exclusively in oocytes. To determine TBP2 function in vivo, we generated TBP2-deficient mice. We found that Tbp2À/À mice are viable with no apparent phenotype. However, females lacking TBP2 are sterile due to defective folliculogenesis, altered chromatin organization, and transcriptional misregulation of key oocyte-specific genes.
    [Show full text]
  • The Genetics of Non-Syndromic Primary Ovarian Insufficiency: a Systematic Review
    Systematic Review The Genetics of Non-Syndromic Primary Ovarian Insufficiency: A Systematic Review Roberta Venturella, M.D.1, Valentino De Vivo, M.D.2, Annunziata Carlea, M.D.2, Pietro D’Alessandro, M.D.2, Gabriele Saccone, M.D.2*, Bruno Arduino, M.D.2, Francesco Paolo Improda, M.D.2, Daniela Lico, M.D.1, Erika Rania, M.D.1, Carmela De Marco, M.D.3, Giuseppe Viglietto, M.D.3, Fulvio Zullo, M.D.1 1. Department of Obstetrics and Gynaecology, Magna Graecia University of Catanzaro, Catanzaro, Italy 2. Department of Neuroscience, Reproductive Sciences and Dentistry, School of Medicine, University of Naples Federico II, Naples, Italy 3. Department of Experimental and Clinical Medicine, Magna Graecia University of Catanzaro, Catanzaro, Italy Abstract Several causes for primary ovarian insufficiency (POI) have been described, including iatrogenic and environmental factor, viral infections, chronic disease as well as genetic alterations. The aim of this review was to collect all the ge- netic mutations associated with non-syndromic POI. All studies, including gene screening, genome-wide study and as- sessing genetic mutations associated with POI, were included and analyzed in this systematic review. Syndromic POI and chromosomal abnormalities were not evaluated. Single gene perturbations, including genes on the X chromosome (such as BMP15, PGRMC1 and FMR1) and genes on autosomal chromosomes (such as GDF9, FIGLA, NOBOX, ESR1, FSHR and NANOS3) have a positive correlation with non-syndromic POI. Future strategies include linkage analysis of families with multiple affected members, array comparative genomic hybridization (CGH) for analysis of copy number variations, next generation sequencing technology and genome-wide data analysis.
    [Show full text]
  • NOBOX (D-3): Sc-390016
    SANTA CRUZ BIOTECHNOLOGY, INC. NOBOX (D-3): sc-390016 BACKGROUND APPLICATIONS Early ovarian folliculogenesis is characterized by the breakdown of germ cell NOBOX (D-3) is recommended for detection of NOBOX of mouse, rat and clusters and formation of primordial follicles. The cessation of ovarian function human origin by Western Blotting (starting dilution 1:100, dilution range under the age of 40 years results in premature ovarian failure (POF) and is 1:100-1:1000), immunoprecipitation [1-2 µg per 100-500 µg of total protein accompanied by amenorrhea, hypoestrogenism and elevated serum gonado- (1 ml of cell lysate)], immunofluorescence (starting dilution 1:50, dilution tropin concentrations. 1% of all women are affected by POF, and mutations in range 1:50-1:500) and solid phase ELISA (starting dilution 1:30, dilution a few genes, including inhibina, fsh receptor and the LH/choriogonadotropin range 1:30-1:3000). receptor have been linked to POF. In addition, several germ cell specific genes Suitable for use as control antibody for NOBOX siRNA (h): sc-89594, and downstream transcription factors are thought to play and important role NOBOX siRNA (m): sc-150015, NOBOX shRNA Plasmid (h): sc-89594-SH, in human oogenesis. NOBOX (newborn ovary homeobox gene), an ooctye-spe- NOBOX shRNA Plasmid (m): sc-150015-SH, NOBOX shRNA (h) Lentiviral cific homeobox gene, is a critical protein involved in early folliculogenesis. Particles: sc-89594-V and NOBOX shRNA (m) Lentiviral Particles: Missense mutations have been shown to cause nonsyndromic ovarian failure sc-150015-V. by disrupting the NOBOX proteins ability to bind to NOBOX DNA-binding ele- ment (NBE), and thereby inhibiting its regulation of Pou5f1 and GDF-9.
    [Show full text]
  • Next Generation Sequencing(Next Gen) Sunquest: NGS
    UNIVERSITY OF MINNESOTA PHYSICIANS OUTREACH LABS Submit this form along with the appropriate Molecular requisition (Molecular Diagnostics or MOLECULAR DIAGNOSTICS (612) 273-8445 Molecular NGS Oncology). DATE: TIME COLLECTED: PCU/CLINIC: AM PM PATIENT IDENTIFICATION DIAGNOSIS (Dx) / DIAGNOSIS CODES (ICD-9) - OUTPATIENTS ONLY SPECIMEN TYPE: o Blood (1) (2) (3) (4) PLEASE COLLECT 5-10CC IN ACD-A OR EDTA TUBE ORDERING PHYSICIAN NAME AND PHONE NUMBER: Tests can be ordered as a full panel, or by individual gene(s). Please contact the genetic counselor with any questions at 612-624-8948 or by pager at 612-899-3291. _______________________________________________ Test Ordered- EPIC: Next generation sequencing(Next Gen) Sunquest: NGS 17-beta-hydroxysteroid dehydrogenase Diabetes mellitus, transient neonatal, 1 Hyperthyroidism, nonautoimmune X deficiency ZFP57 TSHR HSD17B10 Insulin resistance, severe, digenic Hypogonadotropic hypogonadism Adrenal hyperplasia, congenita PPP1R3A Full panel Full panel PPARG CYP17A1 TAC3 Maturity-onset diabetes of the young CYP11B1 TACR3 Full panel CYP11A1 GNRH1 HNF4A Adrenocorticotropic hormone deficiency KISS1 GCK TBX19 WDR11 HNF1A Apparent mineralcorticoid excess HS6ST1 PDX1 HSD11B2 FGFR1 PAX4 Autoimmune polyendocrinopathy PROKR2 NEUROD1 syndrome PROK2 KLF11 AIRE CHD7 ACTH-independent macronodular CEL FGF8 adrenal hyperplasia INS GNRHR GNAS BLK Congenital hypothyroidism KISS1R Estrogen resistance PAX8 NSMF ESR1 Corticosteroid-binding globulin POLR3B ESR2 deficiency Hypoparathyroidism Glucocorticoid deficiency SERPINA6
    [Show full text]