Skip to main content
Log in

Conservation of a Pumilio-Nanos complex from Drosophila germ plasm to human germ cells

Development Genes and Evolution Aims and scope Submit manuscript

Abstract

Germ cells are the cells which ultimately give rise to mature sperm and eggs. In model organisms such as flies and worms, several genes that are required for formation and maintenance of germ cells have been identified and their interactions are rapidly being delineated. By contrast, little is known of the genes required for development of human germ cells and it is not clear whether findings from model organisms will translate into knowledge of human germ cell development, especially given observations that reproductive pathways may evolve more rapidly than somatic pathways. The Pumilio and Nanos genes have been especially well-characterized in model organisms and encode proteins that interact and are required for development of germ stem cells in one or both sexes. Here we report the first characterization of a mammalian Nanos homolog, human NANOS1 (NOS1). We show that human NOS1 protein interacts with the human PUMILIO-2 (PUM2) protein via highly conserved domains to form a stable complex. We also show that in men, the NOS1 and PUM2 proteins are particularly abundant in germline stem cells. These observations mirror those in distant species and document for the first time a conserved protein-protein interaction in germ cells from flies to humans. These results suggest the possibility that the interaction of PUM2 and NOS1 may play a conserved role in germ cell development and maintenance in humans as in model organisms.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price includes VAT (France)

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1A–E.
Fig. 2.
Fig. 3.A–D
Fig. 4A–E.

References

  • Asaoka M, Sano H, Obara Y, Kobayashi S (1998) Maternal Nanos regulates zygotic gene expression in germline progenitors of Drosophila melanogaster. Mech Dev 78:153–158

    Article  CAS  PubMed  Google Scholar 

  • Asaoka-Taguchi M, Yamada M, Nakamura A, Hanyu K, Kobayashi S (1999) Maternal Pumilio acts together with Nanos in germline development in Drosophila embryos. Nature Cell Biol 1:431–437

    Article  CAS  Google Scholar 

  • Bhat KM (1999) The posterior determinant gene nanos is required for the maintenance of the adult germline stem cells during Drosophila oogenesis. Genetics 151:1479–1492

    CAS  PubMed  Google Scholar 

  • Burgoyne PS (1987) The role of the mammalian Y chromosome in spermatogenesis. Development Suppl 101:133–141

    Google Scholar 

  • Castrillon DH, Quade BJ, Wang TY, Quigley C, Crum CP (2000) The human VASA gene is specifically expressed in the germ cell lineage. Proc Natl Acad Sci USA 97:9585–9590

    Article  CAS  PubMed  Google Scholar 

  • Chandley AC (1979) The chromosomal basis of human infertility. Br Med Bull 35:181–186

    CAS  PubMed  Google Scholar 

  • Crittenden SL, Bernstein D, Bachorik J, Thompson B, Moulder G, Barstead R, Wickens M, Kimble J (2002) FBF and control of germline stem cells in Caenorhabditis elegans. Nature 417:600–603

    Article  Google Scholar 

  • Curtis D, Apfeld J, Lehmann R (1995) Nanos is an evolutionarily conserved organizer of anterior-posterior polarity. Development 121:1899–1910

    CAS  PubMed  Google Scholar 

  • Davison RM, Davis CJ, Conway GS (1999) The X chromosome and ovarian failure. Clin Endocrinol 51:673–679

    CAS  Google Scholar 

  • Deshpande G, Calhoun G, Yanowitz JL, Schedl PD (1999) Novel functions of nanos in downregulating mitosis and transcription during the development of the Drosophila germline. Cell 99:271–281

    CAS  PubMed  Google Scholar 

  • Dorfman DM, Genest DR, Reijo Pera RA (1999) Human DAZL1 encodes a candidate fertility factor in women that localizes to the prenatal and postnatal germ cells. Hum Reprod 14:2531–2536

    Google Scholar 

  • Forbes A, Lehmann R (1998) Nanos and Pumilio have critical roles in the development and function of Drosophila germline stem cells. Development 125:679–690

    CAS  PubMed  Google Scholar 

  • Hendry AP, Wenburg JK, Bentzen P, Volk EC, Quinn TP (2000) Rapid evolution of reproductive isolation in the wild: evidence from introduced salmon. Science 290:516–518

    Article  CAS  PubMed  Google Scholar 

  • Houston DW, King ML (2000) A critical role for Xdazl, a germ plasm-localized RNA, in the differentiation of primordial germ cells in Xenopus. Development 127:447–456

    CAS  PubMed  Google Scholar 

  • Houston DW, Zhang J, Maines JZ, Wasserman SA, King ML (1998) A Xenopus DAZ-like gene encodes an RNA component of germ plasm and is a functional homologue of Drosophila boule. Development 125:171–180

    CAS  PubMed  Google Scholar 

  • Kobayashi S, Yamada M, Asaoka M, Kitamura T (1996) Essential role of the posterior morphogen nanos for germline development in Drosophila. Nature 380:708–711

    CAS  PubMed  Google Scholar 

  • Koprunner M, Thisse C, Thisse B, Raz E (2001) A zebrafish nanos-related gene is essential for the development of primordial germ cells. Genes Dev 15:2877–2885

    CAS  PubMed  Google Scholar 

  • Lahn BT, Page DC (1997) Functional coherence of the human Y chromosome. Science 278:675–680

    Article  CAS  PubMed  Google Scholar 

  • Lawson KA, Dunn NR, Roelen BAJ, Zeinstra LM, Davis AM, Wright CVE, Korving JPWFM, Hogan BLM (1999) Bmp4 is required for the generation of primordial germ cells in the mouse embryo. Genes Dev 13:424–436

    CAS  PubMed  Google Scholar 

  • Lehmann R, Nusslen-Volhard C (1987) Involvement of the Pumilio gene in the transport of an abdominal signal in the Drosophila embryo. Nature 329:167–170

    Google Scholar 

  • Lin H, Spradling AC (1997) A novel group of pumilio mutations affects the asymmetric division of germline stem cells in the Drosophila ovary. Development 124:2463–2476

    CAS  PubMed  Google Scholar 

  • Maegawa S, Yasuda K, Inoue K (1999) Maternal mRNA localization of zebrafish DAZ-like gene. Mech Dev 81:223–226

    Article  CAS  PubMed  Google Scholar 

  • Mochizuki K, Sano H, Kobayashi S, Nishimiya-Fujisawa C, Fujisawa T (2000) Expression and evolutionary conservation of nanos-related genes in Hydra. Dev Genes Evol 210:591–602

    Article  CAS  PubMed  Google Scholar 

  • Moore FL, Jaruzelska J, Fox MS, Urano J, Firpo MT, Turek PJ, Dorfman DM, Reijo Pera RA (2003) A human homologue of Drosophila Pumilio is expressed in embryonic stem cells and germ cells and interacts with DAZ (Deleted in AZoospermia) protein. Proc Natl Acad Sci USA 100:538–543

    Google Scholar 

  • Mosquera L, Forristall C, Zhou Y, King ML (1993) A mRNA localized to the vegetal cortex of Xenopus oocytes encodes a protein with a nanos-like zinc finger domain. Development 117:377–386

    CAS  PubMed  Google Scholar 

  • Murata Y, Wharton RP (1995) Binding of Pumilio to maternal hunchback mRNA is required for posterior patterning in Drosophila embryos. Cell 80:747–756

    CAS  PubMed  Google Scholar 

  • Nakahata S, Katsu Y, Mita K, Inoue K, Nagahama Y, Yamashita M (2001) Biochemical identification of Xenopus Pumilio as a sequence-specific cyclin B1 mRNA-binding protein that physically interacts with a Nanos homolog, Xcat-2, and a cytoplasmic polyadenylation element-binding protein. J Biol Chem 276:20945–20953

    Article  CAS  PubMed  Google Scholar 

  • Parisi M, Lin H (1999) The Drosophila Pumilio gene encodes two functional protein isoforms that play multiple roles in germline development, gonadogenesis, oogenesis, and embryogenesis. Genetics 153:235–250

    CAS  PubMed  Google Scholar 

  • Reijo R, Lee TY, Salo P, Alagappan R, Brown LG, Rosenberg M, Rozen S, Jaffe T, Straus D, Hovatta O, et al (1995) Diverse spermatogenic defects in humans caused by Y chromosome deletions encompassing a novel RNA-binding protein gene. Nature Genet 10:383–393

    CAS  PubMed  Google Scholar 

  • Reijo RA, Dorfman DM, Slee R, Renshaw AA, Loughlin KR, Cooke H, Page DC (2000) DAZ family proteins exist throughout male germ cell development and transit from nucleus to cytoplasm at meiosis in humans and mice. Biol Reprod 63:1490–1496

    CAS  PubMed  Google Scholar 

  • Rongo C, Broihier HT, Moore L, Van Doren M, Forbes A, Lehmann R (1997) Germ plasm assembly and germ cell migration in Drosophila. Cold Spring Harbor Symp Quant Biol 62:1–11

    CAS  PubMed  Google Scholar 

  • Seydoux G, Mello CC, Pettitt J, Wood WB, Preiss JR, Fire A (1996) Repression of gene expression in the embryonic germ lineage of C. elegans. Nature 382:713–716

    Google Scholar 

  • Sonoda J, Wharton RP (1999) Recruitment of Nanos to hunchback mRNA by Pumilio. Genes Dev 13:2704–2712

    Article  CAS  PubMed  Google Scholar 

  • Subramaniam K, Seydoux G (1999) nos-1 and nos-2, two genes related to Drosophila nanos, regulate primordial germ cell development and survival in Caenorhabditis elegans. Development 126:4861–4871

    CAS  PubMed  Google Scholar 

  • Swanson WJ, Vacquier VD (2002) The rapid evolution of reproductive proteins. Nature Rev Genet 3:137–144

    Article  CAS  Google Scholar 

  • Tanaka SS, Toyooka Y, Akasu R, Katoh-Fukui Y, Nakahara Y, Suzuki R, Yokoyama M, Noce T (2000) The mouse homolog of Drosophila Vasa is required for the development of male germ cells. Genes Dev 14:841–853

    CAS  PubMed  Google Scholar 

  • Wang C, Lehmann R (1991) Nanos is the localized posterior determinant in Drosophila. Cell 68:1177

    Google Scholar 

  • Wreden C, Verrotti AC, Schisa JA, Lieberfarb ME, Strickland S (1997) Nanos and pumilio establish embryonic polarity in Drosophila by promoting posterior deadenylation of hunchback mRNA. Development 124:3015–3023

    CAS  PubMed  Google Scholar 

  • Wyckoff GJ, Wang W, Wu C-I (2000) Rapid evolution of male reproductive genes in the descent of man. Nature 403:304–309

    Article  PubMed  Google Scholar 

  • Wylie C (2000) Germ cells. Curr Opin Genet Dev 10:410–413

    Article  CAS  PubMed  Google Scholar 

  • Ying Y, Qi X, Zhao G-Q (2001) Induction of primordial germ cells from murine epiblasts by synergistic action of BMP4 and BMP8B signaling pathways. Proc Natl Acad Sci USA 98:7858–7862

    Article  CAS  PubMed  Google Scholar 

  • Zamore PD, Williamson JR, Lehmann R (1997) The Pumilio protein binds RNA through a conserved domain that defines a new class of RNA-binding proteins. RNA 3:1421–1433

    CAS  PubMed  Google Scholar 

  • Zamore PD, Bartel DP, Lehmann R, Williamson JR (1999) The PUMILIO-RNA interaction: a single RNA-binding domain monomer recognizes a bipartite target sequence. Biochem 38:596–604

    Article  CAS  Google Scholar 

  • Zhou Y, King ML (1996) RNA transport to the vegetal cortex of Xenopus oocytes. Development 179:173–183

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We thank Maria M. Konarska, Daniel F. Ortiz, Krzysztof Kula, Frederick L. Moore, Eugene Y. Xu, and Mark S. Fox for helpful discussions. This work was supported by grants from the Howard Hughes Medical Institute (M.K.), the Polish State Committee for Scientific Research (P05E 018 33 to J.J. and 6 P05E 001 21 to K.K.) and the National Institutes of Health, the Searle Foundation and the Sandler Family Foundation (R.A.R.P.).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Renee A. Reijo Pera.

Additional information

Edited by D.A. Weisblat

Rights and permissions

Reprints and permissions

About this article

Cite this article

Jaruzelska, J., Kotecki, M., Kusz, K. et al. Conservation of a Pumilio-Nanos complex from Drosophila germ plasm to human germ cells. Dev Genes Evol 213, 120–126 (2003). https://doi.org/10.1007/s00427-003-0303-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00427-003-0303-2

Keywords

Navigation