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Vol. 16, No. 22, pp. 2849-2864, November 15, 2002
1 Department of Molecular and Cellular Biology, The
Biolabs, Harvard University, Cambridge, Massachusetts 02138, USA
The hedgehog signaling pathway organizes the developing ventral
neural tube by establishing distinct neural progenitor fates along the
dorsoventral axis. Smoothened (Smo) is essential for all Hedgehog (Hh) signaling, and genetic inactivation of Smo
cells autonomously blocks the ability of cells to transduce the Hh
signal. Using a chimeric approach, we examined the behavior of
Smo null mutant neural progenitor cells in the developing
vertebrate spinal cord, and we show that direct Hh signaling is
essential for the specification of all ventral progenitor populations.
Further, Hh signaling extends into the dorsal half of the spinal cord
including the intermediate Dbx expression domain. Surprisingly, in the
absence of Sonic hedgehog (Shh), we observe the presence of a
Smo-dependent Hh signaling activity operating in the ventral half of
the spinal cord that most likely reflects Indian hedgehog (Ihh)
signaling originating from the underlying gut endoderm. Comparative
studies of Shh, Smo, and Gli3 single and
compound mutants reveal that Hh signaling acts in part to specify
neural cell identity by counteracting the repressive action of Gli3 on
p0, p1, p2, and pMN formation. However, whereas these cell identities
are restored in Gli3/Smo compound mutants, correct
stratification of the rescued ventral cell types is lost. Thus, Hh
signaling is essential for organizing ventral cell pattern, possibly
through the control of differential cell affinities.
[Key Words: Smoothened; neural tube; patterning; Gli3; cell affinity; Mouse]
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