Nanog expression in mouse germ cell development.

Nanog is a newly identified transcriptional factor bearing a homeodomain and expressed in pluripotential cells of preimplantation and early postimplantation embryos, and embryonic stem (ES) and embryonic germ (EG) cells. Knockout experiments indicate that Nanog functions as a key player in maintaining the pluripotency of stem cells. Importantly, Nanog expression is highly expressed in primordial germ cells (PGCs) of E11.5 and E12.5 mouse embryos. However, its temporal and spatial expression pattern and function in germ cells are largely unknown. To address these issues, whole embryos and cryosections of embryos were immunostained with anti-NANOG and anti-STELLA/PGC7 antibodies. NANOG expression, repressed in colonized PGCs of E7.25-E7.5 embryos, became detectable in migrating PGCs of E7.75-E8.0 embryos. Both male and female PGCs migrating in E9.5 and E10.5 embryos and colonizing the genital ridges of E11.5 and E12.5 embryos were positive for NANOG immunostaining, while the NANOG expression pattern differed between the sexes in the later developmental stage. In female gonadal PGCs of E13.5 and E14.5 embryos, NANOG became undetectable in germ cells positive for the synaptonemal complex-specific protein SCP3, while in male PGCs of E14.5-E16.5 embryos, the number of NANOG-positive germ cells drastically decreased during the mitotic arrest. No germ cells positive for NANOG were detectable in testes and ovaries of adult mice. Thus, in germ cell development, NANOG is expressed in proliferating germ cells, in which nuclear reprogramming is progressing.

[1]  Y. Matsui,et al.  Regulation of expression of mouse interferon‐induced transmembrane protein like gene‐3, Ifitm3 (mil‐1, fragilis), in germ cells , 2004, Developmental dynamics : an official publication of the American Association of Anatomists.

[2]  P. Donovan,et al.  Long-term proliferation of mouse primordial germ cells in culture , 1992, Nature.

[3]  Philippe Soriano,et al.  Tissue non-specific alkaline phosphatase is expressed in both embryonic and extraembryonic lineages during mouse embryogenesis but is not required for migration of primordial germ cells. , 1995, Development.

[4]  R. Lovell-Badge,et al.  Multipotent cell lineages in early mouse development depend on SOX2 function. , 2003, Genes & development.

[5]  A. Mclaren,et al.  Primordial germ cells in the mouse embryo during gastrulation. , 1990, Development.

[6]  M. Oshimura,et al.  Generation of Pluripotent Stem Cells from Neonatal Mouse Testis , 2004, Cell.

[7]  M. Surani,et al.  A molecular programme for the specification of germ cell fate in mice , 2002, Nature.

[8]  Ming-Shiun Tsai,et al.  A novel NK-type homeobox gene, ENK (early embryo specific NK), preferentially expressed in embryonic stem cells. , 2003, Gene expression patterns : GEP.

[9]  N. Nakatsuji,et al.  Autonomous transition into meiosis of mouse fetal germ cells in vitro and its inhibition by gp130-mediated signaling. , 2001, Developmental biology.

[10]  B. Hogan,et al.  Derivation of pluripotential embryonic stem cells from murine primordial germ cells in culture , 1992, Cell.

[11]  Y. Nishimune,et al.  A germ cell-specific nuclear antigen recognized by a monoclonal antibody raised against mouse testicular germ cells. , 1998, International journal of andrology.

[12]  M. Tada,et al.  Octamer and Sox Elements Are Required for Transcriptional cis Regulation of Nanog Gene Expression , 2005, Molecular and Cellular Biology.

[13]  M. Tada,et al.  Pluripotential competence of cells associated with Nanog activity , 2005, Mechanisms of Development.

[14]  H. Schöler,et al.  Germline‐specific expression of the Oct‐4/green fluorescent protein (GFP) transgene in mice , 1999, Development, growth & differentiation.

[15]  M. Murakami,et al.  The Homeoprotein Nanog Is Required for Maintenance of Pluripotency in Mouse Epiblast and ES Cells , 2003, Cell.

[16]  A. Hart,et al.  Identification, cloning and expression analysis of the pluripotency promoting Nanog genes in mouse and human , 2004, Developmental dynamics : an official publication of the American Association of Anatomists.

[17]  X. Qi,et al.  Induction of primordial germ cells from murine epiblasts by synergistic action of BMP4 and BMP8B signaling pathways , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[18]  J. Nichols,et al.  Functional Expression Cloning of Nanog, a Pluripotency Sustaining Factor in Embryonic Stem Cells , 2003, Cell.

[19]  B. Hogan,et al.  Bmp4 is required for the generation of primordial germ cells in the mouse embryo. , 1999, Genes & development.