TY - JOUR
T1 - L3/Lhx8 is a pivotal factor for cholinergic differentiation of murine embryonic stem cells
AU - Manabe, T.
AU - Tatsumi, K.
AU - Inoue, M.
AU - Makinodan, M.
AU - Yamauchi, T.
AU - Makinodan, E.
AU - Yokoyama, S.
AU - Sakumura, R.
AU - Wanaka, A.
PY - 2007/6
Y1 - 2007/6
N2 - 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.
AB - 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.
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U2 - 10.1038/sj.cdd.4402106
DO - 10.1038/sj.cdd.4402106
M3 - Article
C2 - 17318222
AN - SCOPUS:34249068573
SN - 1350-9047
VL - 14
SP - 1080
EP - 1085
JO - Cell Death and Differentiation
JF - Cell Death and Differentiation
IS - 6
ER -