Numbers game

Although gigantic basketball player Shaquille O'Neal may dwarf us mortals, his cells are no bigger than yours or mine. He just has more of them. But how vertebrates regulate their cell number has been as puzzling as Shaq's inability to shoot free throws. Now, a team of researchers has pinpointed a gene that helps determine body size in vertebrates by controlling cell division. The findings support the notion that vertebrates govern body size by regulating cell number, whereas insects vary both cell size and cell number.

Andreas Trumpp (Swiss Institute for Experimental Cancer Research, Epalinges, Switzerland) and colleagues focused on c-myc, a proto-oncogene that is mutated or overexpressed in ∼20% of human cancers and was suspected to be a cell division regulator. Recent fly studies had challenged this view, says Trumpp. Reducing the levels of dmyc, the fly homologue of c-myc, produced smaller animals that also sported smaller cells, providing strong evidence that the gene's function was to govern cell growth.To check this surprising result, Trumpp and colleagues created transgenic mice with reduced levels of c-Myc. The rodents were smaller than normal, but had normal-sized cells. Studies with T cells were consistent with this function of c-Myc in controlling cell number rather than cell size. Activated T cells balloon before beginning to proliferate, and the authors found that T cells carrying mutant forms of c-myc still underwent this growth spurt but rarely entered the cell cycle. Thus, c-Myc regulates proliferation, ushering cells into the cell cycle and keeping them on the path to division.

Dmyc can stimulate division in mouse cells lacking c-myc. According to Trumpp, this argues that the differences between vertebrates and insects lie in the downstream pathways, although the identities of the target genes remain unknown. ▪

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