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The Notch response inhibitor DAPT enhances neuronal differentiation in embryonic stem cell‐derived embryoid bodies independently of sonic hedgehog signaling
Author(s) -
Crawford T. Quinn,
Roelink Henk
Publication year - 2007
Publication title -
developmental dynamics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.634
H-Index - 141
eISSN - 1097-0177
pISSN - 1058-8388
DOI - 10.1002/dvdy.21083
Subject(s) - sonic hedgehog , embryoid body , biology , embryonic stem cell , notch signaling pathway , microbiology and biotechnology , hedgehog signaling pathway , neural stem cell , hedgehog , precursor cell , stem cell , endocrinology , medicine , signal transduction , cell , adult stem cell , biochemistry , gene
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)‐l‐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. Developmental Dynamics 236:886–892, 2007. © 2007 Wiley‐Liss, Inc.