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First published online April 3, 2008
Stem Cells Vol. 26 No. 6 June 2008, pp. 1490 -1495
doi:10.1634/stemcells.2007-1099; www.StemCells.com
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EMBRYONIC STEM CELLS

The Neuronal Differentiation Potential of Ldb1-Null Mutant Embryonic Stem Cells Is Dependent on Extrinsic Influences

Minyoung Hwanga, Marat Gorivodskyb, Minjung Kimc, Heiner Westphalb, Dongho Geuma

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 {alpha}-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.

Disclosure of potential conflicts of interest is found at the end of this article.







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