The neocortex is the region of the cerebral cortex responsible for higher level cognitive functions, forming about 85% of the human brain. On p. 337, Palma and Ruiz i Altaba report that, during mouse development, endogenous Sonic hedgehog (SHH) signalling regulates the numbers of stem and precursor cells in the neocortex, and hence its ultimate size. The researchers show that SHH is required for the normal proliferation and self-renewal of neocortical neurospheres in culture, acting in cooperation with EGF. In vivo, brain phenotypes in Shh, Gli2 and Gli3 mutants - the GLI transcription factors are mediators of hedgehog signalling - are consistent with reduced numbers of neocortical cells with stem cell properties. The researchers speculate that evolutionary changes in SHH signalling may underlie the different brain sizes and shapes that we see today.
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