Hedgehog makes giant brains

Brain size is kept in check by proteins at cell–cell junctions that act as look-outs for cell density, report Wen-Hui Lien, Olga Klezovitch, Valeri Vasioukhin, and colleagues (Fred Hutchinson Cancer Research Center). The group finds that Hedgehog (Hh)-mediated proliferation is dampened in densely packed cells by an adherens junction component called αE-catenin.

To study the function of adherens junctions, the FHCRC group eliminated αE-catenin, which links the cell junctions to the cytoskeleton. Mutants lacking αE-cadherin in their developing central nervous system had strikingly large brains, with twice as many cells than wild-type controls. Much of this massive—and lethal—excess was due to rapid mitotic cycling of neural progenitor cells.

Microarrays revealed that the expression of fewer than ten genes was altered by the loss of αE-catenin. Several of the up-regulated genes are activators...