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Brain size may depend upon how neural cells are cleaved

be generated during brain development," she said.

Using the embryonic mouse brain as a model, Sanada and Tsai sought to determine whether G proteins play a role in the developing mammalian brain. In their initial experiments, they impaired the function of the Gβγ subunits of heterotrimeric G proteins, in the developing mouse brain. They saw a dramatic interference with orientation of cell cleavage to overproduce "postmitotic" neurons -- cells that could no longer divide -- at the expense of progenitor cells, which could still divide. "This observation led us to want to further test whether impairment of Gβγ has any consequences for cell fate in division, because it has been speculated that the different division planes dictate the ultimate cell fate adoption of daughter cells," said Tsai.

To determine definitively whether impairment of Gβγ had a direct effect on cell fate, the researchers impaired Gβγ signaling in the mouse brains in utero, then isolated the progenitor cells to study the effects in vitro. Those studies revealed that impairing Gβγ did result in overproduction of neurons as a result of both daughter cells adopting the neuronal fate. Thus, the researchers concluded that Gβγ does control the orientation of cleavage and the identity of the daughter cells -- whether they will become neurons or progenitor cells.

Sanada and Tsai also sought to determine how Gβγ is regulated. Studies on asymmetric cell division in fruit flies and roundworms had implicated a particular class of proteins -- known as AGS3 and mPins in mammals -- as upstream regulators of G proteins.

The researchers' analyses showed that AGS3 is, indeed, expressed in progenitor cells. And when they "silenced" AGS3 expression in embryonic mouse brains, the resulting abnormalities mimicked those produced when Gβγ signaling was disrupted.

Now that the role of Gβγ in neural cell proliferation has been discovered, said Tsai, further studies will try to pinpoin
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Source:Howard Hughes Medical Institute


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