New Class Of Molecular Cues Guides Nervous System Wiring

s colleagues were searching for that midline repellent signal and found that the Slit protein prevented neurons that had crossed the midline from crossing back over. Once axons cross the midline, they turn up their levels of Slit receptor (Robo) and this prevents them from crossing again, says Goodman. Thanks to the Slit protein, which Goodman and his colleagues in the first of the three Cell papers call the "midline repellent," the developing brain avoids a tangle of catastrophic miswiring.

These investigators then collaborated with HHMI investigator Marc Tessier-Lavigne and colleagues at the University of California San Francisco to explore Slit's function in mammals, extending the work in Drosophila. In the second Cell paper, predoctoral fellow Katja Brose and others in Tessier-Lavigne’s and Goodman's laboratory reported finding mammalian versions of Slit, which also act as repellents for growing mammalian neurons.

But that was not the end of the Slit story. In a another set of studies, Kuan Hong Wang, an HHMI predoctoral fellow in Tessier-Lavigne’s laboratory, had been working independently at a lab bench next to Brose's for several years on what they thought was a separate project. While Brose was isolating the mammalian versions of Slit in collaboration with the Goodman laboratory, Wang was attempting to isolate an unknown protein that induced branching of neuronal axons, the cable-like structures that neurons grow to establish contacts with other neurons.

When Wang finally isolated the branch-inducing protein and determined its structure, he and Brose realized that their two molecules were basically identical. "At that point, we fell off our chairs," said Tessier-Lavigne. "It's one of those amazing moments in the laboratory when you think you're working on two different things, but in fact you’re working on two different faces of the same thing."

Both Goodman and Tessier-Lavigne view the serendi

Contact: Jim Keeley
Howard Hughes Medical Institute

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