[Frontiers in Bioscience 14, 1068-1087, January 1, 2009]

Specification of the germ cell lineage in mice

Mitinori Saitou1,2

1Laboratory for Mammalian Germ Cell Biology, Center for Developmental Biology, RIKEN Kobe Institute, 2-2-3 Minatojima-Minamimachi, Chuo-ku, Kobe 650-0047, Japan, 2Laboratory of Molecular Cell Biology and Development, Graduate School of Biostudies, Kyoto University, Yoshida-Konoe-cho, Sakyo-ku, Kyoto 606-8501, Japan

TABLE OF CONTENTS

1. Abstract
2. Introduction
3. From fertilization to the specification of the new germ cell lineage
4. Experimental embryology on the origin of the germ cell lineage
5. Signaling for germ cell specification
6. Key molecules and events associated with germ cell specification
6.1. The founder PGCs repress the Hox genes
6.2. Blimp1 is a critical regulator for germ cell specification
6.3. A molecular program for germ cell specification
7. Key molecules and events in PGCs after their specification
7.1. Migration and proliferation of PGCs
7.2. Molecules essential for early PGC development
7.3. PGCs can de-differentiate into pluripotent EG cells in vitro
7.4. Epigenetic reprogramming in migrating PGCs
7.4.1. Genome-wide epigenetic reprogramming in migrating PGCs
7.4.2. Potential significance of epigenetic reprogramming in migrating PGCs
8. PGC specification/development and induced pluripotency in somatic cells
9. Perspective
10. Acknowledgements
11. References

1. ABSTRACT

Specification of the germ cell lineage is fundamental in development and heredity. In mice, and presumably in all mammals, germ cell fate is not an inherited trait from the egg, but is induced in pluripotent epiblast cells by signaling molecules. Recent studies are beginning to uncover the signaling requirements and key transcriptional regulators for the specification of the germ cell lineage in mice, as well as the distinct properties that the specified germ cells acquire uniquely. Accordingly, the evidence suggests that germ cell specification is an integration of the repression of the somatic program, re-acquisition of potential pluripotency, and ensuing genome-wide epigenetic reprogramming. The accumulated knowledge will be critical for the reconstitution of this key lineage in vitro, which may provide a useful foundation for reproductive and regenerative medicine.