Hedgehog signaling is involved in development of the neocortex
2008
Sonic hedgehog (Shh) function is essential for patterning and cell fate
specification, particularly in ventral regions of the central nervous system.
It is also a crucial mitogen for cerebellar granule neuron precursors and is
important in maintenance of the stem cell niche in the postnatal
telencephalon. Although it has been reported that Shh is expressed in
the developing dorsal telencephalon, functions of Shh in this region
are unclear, and detailed characterization of Shh mRNA transcripts in
situ has not been demonstrated. To clarify the roles of Shh signaling in
dorsal pallium (neocortex primordium) development, we have knocked out the
Shh and Smo genes specifically in the early developing
dorsal telencephalon by using Emx1 cre mice. The
mutants showed a smaller dorsal telencephalon at E18.5, which was caused by
cell cycle kinetics defects of the neural progenitor/stem cells. The cell
cycle length of the progenitor/stem cells was prolonged, and the number of
cycle-exiting cells and neurogenesis were decreased. Birth-date analysis
revealed abnormal positioning of neurons in the mutants. The characteristics
of the subventricular zone, ventricular zone and subplate cells were also
affected. Weak immunoreactivity of Shh was detected in the dorsal
telencephalon of wild types. Reduced Shh immunoreactivity in mutant dorsal
telencephalons supports the above phenotypes. Our data indicate that Shh
signaling plays an important role in development of the neocortex.
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