L3/Lhx8 is a pivotal factor for cholinergic differentiation of murine embryonic stem cells |
| |
Authors: | Manabe T Tatsumi K Inoue M Makinodan M Yamauchi T Makinodan E Yokoyama S Sakumura R Wanaka A |
| |
Affiliation: | Department of 2nd Anatomy, Faculty of Medicine, Nara Medical University, 840 Shijyo-cho, Kasihara City, Nara 634-8521, Japan. manabe@cdb.riken.jp |
| |
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. |
| |
Keywords: | |
本文献已被 PubMed 等数据库收录! |
|