Letter

Nature 441, 766-769 (8 June 2006) | doi:10.1038/nature04831; Received 30 September 2005; Accepted 12 April 2006

Germline transmission of genetically modified primordial germ cells

Marie-Cecile van de Lavoir1, Jennifer H. Diamond1, Philip A. Leighton1, Christine Mather-Love1, Babette S. Heyer1, Renee Bradshaw1, Allyn Kerchner1, Lisa T. Hooi1, Terri M. Gessaro2, Susan E. Swanberg2, Mary E. Delany2 and Robert J. Etches1

Primordial germ cells (PGCs) are the precursors of sperm and eggs1. In most animals, segregation of the germ line from the somatic lineages is one of the earliest events in development2; in avian embryos, PGCs are first identified in an extra-embryonic region, the germinal crescent, after approximately 18 h of incubation. After 50–55 h of development, PGCs migrate to the gonad and subsequently produce functional sperm and oocytes3, 4. So far, cultures of PGCs that remain restricted to the germ line have not been reported in any species5, 6. Here we show that chicken PGCs can be isolated, cultured and genetically modified while maintaining their commitment to the germ line. Furthermore, we show that chicken PGCs can be induced in vitro to differentiate into embryonic germ cells that contribute to somatic tissues. Retention of the commitment of PGCs to the germ line after extended periods in culture and after genetic modification combined with their capacity to acquire somatic competence in vitro provides a new model for developmental biology. The utility of the model is enhanced by the accessibility of the avian embryo, which facilitates access to the earliest stages of development and supplies a facile route for the reintroduction of PGCs into the embryonic vasculature. In addition, these attributes create new opportunities to manipulate the genome of chickens for agricultural and pharmaceutical applications.

  1. Origen Therapeutics, 1450 Rollins Road, Burlingame, California 94010, USA
  2. Department of Animal Science, 1 Shields Avenue, University of California, Davis, 2131D Meyer Hall, Davis, California 95616, USA

Correspondence to: Robert J. Etches1 Correspondence and requests for materials should be addressed to R.J.E. (Email: retches@origentherapeutics.com).

Received 30 September 2005 | Accepted 12 April 2006

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