L3/Lhx8 is a pivotal factor for cholinergic differentiation of murine embryonic stem cells

T. Manabe, K. Tatsumi, M. Inoue, M. Makinodan, T. Yamauchi, E. Makinodan, S. Yokoyama, R. Sakumura, A. Wanaka

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35 Citations (Scopus)

Abstract

L3/Lhx8 is a member of the LIM-homeobox gene family. Previously, we demonstrated that L3/Lhx8-null mice specifically lacked cholinergic neurons in the basal forebrain. In the present study, we conditionally suppressed L3/Lhx8 function during retinoic acid-induced neural differentiation of a murine embryonic stem (ES) cell line using an L3/ Lhx8-targeted small interfering RNA (siRNA) produced by an H1.2 promoter-driven vector. Our culture conditions induced efficient differentiation of the ES cells into neurons and astrocytes, but far less efficient differentiation into oligodendrocytes. Suppression of L3/ Lhx8 expression by siRNA led to a dramatic decrease in the number of cells positive for the cholinergic marker ChAT, and overexpression of L3/ Lhx8 recovered this effect. However, no significant changes were observed in the number of Tuj1+ neurons and GABA+ cells. These results strongly suggest that L3/Lhx8 is a key factor in the cholinergic differentiation of murine ES cells and is involved in basal forebrain development.

Original languageEnglish
Pages (from-to)1080-1085
Number of pages6
JournalCell Death and Differentiation
Volume14
Issue number6
DOIs
Publication statusPublished - 06-2007
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cell Biology

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