The Notch response inhibitor DAPT enhances neuronal differentiation in embryonic stem cell-derived embryoid bodies independently of Sonic Hedgehog signaling

被引:87
作者
Crawford, T. Quinn [1 ]
Roelink, Henk [1 ]
机构
[1] Univ Washington, Dept Biol Struct, Seattle, WA 98195 USA
关键词
Shh; Smo; Ptc1; Notch; DAPT; ES cells; embryoid bodies; neuronal differentiation;
D O I
10.1002/dvdy.21083
中图分类号
R602 [外科病理学、解剖学]; R32 [人体形态学];
学科分类号
100101 ;
摘要
During development of the neural tube, inhibition of the Notch response as well as the activation of the Sonic Hedgehog (Shh) response results in the formation of neuronal cell types. To determine whether Shh and Notch act independently, we tested the effects of the Notch inhibitor DAPT (N-[N-(3,5-difluorophenacetyl)-1-alanyl]-S-phenylglycine t-butyl ester) on neuralized, embryonic stem (ES) cell-derived embryoid bodies (EBs), while varying the levels of Shh pathway activation. Shh-resistant EBs were derived from Smo null ES cells, while EBs with constitutive high level of Shh pathway activation were derived from Ptc1 null ES cells. Intermediate levels of Shh pathway activation was achieved by the addition of ShhN to the EB culture medium. It was found that DAPT-mediated inhibition of the Notch response resulted in enhanced neuronal differentiation. In the absence of Shh, more interneurons were detected, while the main effect of DAPT on EBs with an activated Shh response was the precocious loss of ventral neuronal precursor-specific markers.
引用
收藏
页码:886 / 892
页数:7
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