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Parga JA, Rodriguez-Pallares J, Blanco V, Guerra
MJ, Labandeira-Garcia JL.
Different effects of anti-sonic
hedgehog antibodies and the hedgehog pathway
inhibitor cyclopamine on generation of
dopaminergic neurons from neurospheres of
mesencephalic precursors.
Dev Dyn. 2008 Apr;237(4):909-17
Laboratory of Neuroanatomy and Experimental Neurology,
Department of Morphological Sciences, Faculty of Medicine,
University of Santiago de Compostela, Santiago de Compostela,
Spain.
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. (c) 2008
Wiley-Liss, Inc.
PMID: 18330924
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