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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
Author(s) -
Parga J.A.,
RodriguezPallares J.,
Blanco V.,
Guerra M. J.,
LabandeiraGarcia J. L.
Publication year - 2008
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.21481
Subject(s) - cyclopamine , smoothened , sonic hedgehog , hedgehog signaling pathway , dopaminergic , neurosphere , biology , serotonergic , neuroscience , hedgehog , patched , dopaminergic pathways , gabaergic , microbiology and biotechnology , dopamine , signal transduction , cellular differentiation , genetics , inhibitory postsynaptic potential , receptor , serotonin , adult stem cell , gene
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.