Understanding the molecular mechanisms of stem cell maintenance
Lu Teng1,*,, Nathan A. Mundell2,4,, Audrey Y. Frist3,4, Qiaohong Wang1 and Patricia A. Labosky1,2,3,4,
1 Department of Cell and Developmental Biology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104-6058, USA.
2 Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, TN 37232-0494, USA.
3 Department of Cell and Developmental Biology, Vanderbilt University School of Medicine, Nashville, TN 37232-0494, USA.
4 Center for Stem Cell Biology, Vanderbilt University School of Medicine, Nashville, TN 37232-0494, USA.
Author for correspondence (e-mail: trish.labosky@vanderbilt.edu)
Accepted 28 February 2008
Understanding the molecular mechanisms of stem cell maintenance is crucial for the ultimate goal of manipulating stem cells for the treatment of disease. Foxd3 is required early in mouse embryogenesis; Foxd3-/- embryos fail around the time of implantation, cells of the inner cell mass cannot be maintained in vitro, and blastocyst-derived stem cell lines cannot be established. Here, we report that Foxd3 is required for maintenance of the multipotent mammalian neural crest. Using tissue-specific deletion of Foxd3 in the neural crest, we show that Foxd3flox/-; Wnt1-Cre mice die perinatally with a catastrophic loss of neural crest-derived structures. Cranial neural crest tissues are either missing or severely reduced in size, the peripheral nervous system consists of reduced dorsal root ganglia and cranial nerves, and the entire gastrointestinal tract is devoid of neural crest derivatives. These results demonstrate a global role for this transcriptional repressor in all aspects of neural crest maintenance along the anterior-posterior axis, and establish an unprecedented molecular link between multiple divergent progenitor lineages of the mammalian embryo.
Key words: Neural crest, Foxd3, Mouse embryo, Stem cell maintenance