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EMBRYONIC STEM CELLS |
aGraduate School of Medicine, Korea University, Seoul, Korea;
Laboratories of bMammalian Genes and Development and
cMolecular Genetics, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland, USA
Key Words. Ldb1 • Embryonic stem cells • Neuronal differentiation • Embryoid body • Five-stage method • Adherent monolayer culture method
Correspondence: Heiner Westphal, M.D., Ph.D., Laboratory of Mammalian Genes and Development, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892-2790, USA. Telephone: 301-496-1855; Fax: 301-402-0543; e-mail: hw{at}helix.nih.gov; or Dongho Geum, Ph.D., Graduate School of Medicine, Brain Korea 21, Korea University, Seoul 136-705, South Korea. Telephone: 82-2-920-6091; Fax: 82-2-929-5696; e-mail: geumd{at}korea.ac.kr
Received January 8, 2008;
accepted for publication March 19, 2008.
First published online in STEM CELLS EXPRESS April 3, 2008.
LIM-domain binding protein 1 (Ldb1) is a multiadaptor protein that mediates the action of transcription factors, including LIM-homeodomain proteins. To elucidate the functional role of Ldb1 in the neuronal differentiation of embryonic stem (ES) cells, we have generated Ldb1-null mutant (Ldb1–/–) ES cells and examined neuronal differentiation potentials in vitro using two different neuronal differentiation protocols. When subjected to a five-stage protocol that recapitulates in vivo conditions of neuronal differentiation, wild-type ES cells differentiated into a wide spectrum of neuronal cell types. However, Ldb1–/– ES cells did not differentiate into neuronal cells; instead, they differentiated into sarcomeric
Disclosure of potential conflicts of interest is found at the end of this article.
-actinin-positive muscle cells. In contrast, when an adherent monolayer culture procedure (which is based on the default mechanism of neural induction and eliminates environmental influences) was applied, both wild-type and Ldb1–/– ES cells differentiated into MAP2-positive mature neurons. Comparison of the results obtained when two different neuronal differentiation protocols were used suggests that Ldb1–/– ES cells have an innate potential to differentiate into neuronal cells, but this potential can be inhibited by environmental influences.
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