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Different effects of anti‐sonic hedgehog antibodies and the hedgehog pathway inhibitor cyclopamine on generation of dopaminergic neurons from neurospheres of mesencephalic precursors

Different effects of anti‐sonic hedgehog antibodies and the hedgehog pathway inhibitor... Production of dopaminergic neurons from stem/precursor cells for transplantation in Parkinson's disease has become a major focus of research. However, the inductive signals mediating this process have not been clarified. Reported data on the effects of Sonic hedgehog on differentiation of dopaminergic and serotonergic neurons from cultures of neural precursors are controversial. In the present study, cultures of proliferating neurospheres of mesencephalic precursors treated with anti–sonic hedgehog antibodies showed significantly less serotonergic and GABAergic cells and a markedly higher number of dopaminergic neurons generated from the neurospheres than control cultures. Treatment of the neurospheres with cyclopamine, which selectively inhibits sonic hedgehog signaling by preventing Smoothened activation, did not induce significant changes in generation of serotonergic and dopaminergic neurons. This suggests that Smoothened activation is not significantly involved in the above‐mentioned effects and that sonic hedgehog may exert effects on the mesencephalic precursors that do not involve the canonical Patched‐Smoothened‐Gli signaling. Developmental Dynamics 237:909–917, 2008. © 2008 Wiley‐Liss, Inc. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Developmental Dynamics Wiley

Different effects of anti‐sonic hedgehog antibodies and the hedgehog pathway inhibitor cyclopamine on generation of dopaminergic neurons from neurospheres of mesencephalic precursors

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References (55)

Publisher
Wiley
Copyright
Copyright © 2008 Wiley‐Liss, Inc.
ISSN
1058-8388
eISSN
1097-0177
DOI
10.1002/dvdy.21481
pmid
18330924
Publisher site
See Article on Publisher Site

Abstract

Production of dopaminergic neurons from stem/precursor cells for transplantation in Parkinson's disease has become a major focus of research. However, the inductive signals mediating this process have not been clarified. Reported data on the effects of Sonic hedgehog on differentiation of dopaminergic and serotonergic neurons from cultures of neural precursors are controversial. In the present study, cultures of proliferating neurospheres of mesencephalic precursors treated with anti–sonic hedgehog antibodies showed significantly less serotonergic and GABAergic cells and a markedly higher number of dopaminergic neurons generated from the neurospheres than control cultures. Treatment of the neurospheres with cyclopamine, which selectively inhibits sonic hedgehog signaling by preventing Smoothened activation, did not induce significant changes in generation of serotonergic and dopaminergic neurons. This suggests that Smoothened activation is not significantly involved in the above‐mentioned effects and that sonic hedgehog may exert effects on the mesencephalic precursors that do not involve the canonical Patched‐Smoothened‐Gli signaling. Developmental Dynamics 237:909–917, 2008. © 2008 Wiley‐Liss, Inc.

Journal

Developmental DynamicsWiley

Published: Apr 1, 2008

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