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

¹ Graduate School of Medicine, Korea University, Seoul 136-705, Korea; National Institute of Health, Bethesda, MD 20892, USA
² Laboratory of Mammalian Genes and Development, National Institute of Health, Bethesda, MD 20892, USA
³ Laboratory of Molecular Genetics, National Institute of Child health and Human Development, National Institute of Health, Bethesda, MD 20892, USA

^* To whom correspondence should be addressed. E-mail: geumd{at}korea.ac.kr.

Correspondence may also be addressed to Heiner Westphal at hw@helix.nih.gov

	Abstract

Ldb1 is a multi-adaptor 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-step protocol which 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 -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) is 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 are used suggests that Ldb1-/- ES cells have an innate potential to differentiate into neuronal cells, but this potential can be inhibited by environmental influences.