Molecular Genetics

Building a Brain Map

Science's STKE  13 Mar 2001:
Vol. 2001, Issue 73, pp. tw3
DOI: 10.1126/stke.2001.73.tw3

Leighton et al. developed a sophisticated screen to specifically detect mouse proteins that function in axonal guidance. To identify cell-surface and secreted proteins, which would include receptors and ligands that contribute to proper patterning in the brain, they used a gene trapping strategy that selects for vector insertion into a gene that encodes a signal sequence. To identify axons expressing such targeted genes, they included an internal ribosome entry site (IRES) to drive the expression of placental alkaline phosphatase (PLAP), a convenient axonal marker. Such labeling of axons allowed visualization of the wiring pattern of altered cells in the brains of transgenic mice. Among the targeted genes, the authors identified those encoding semaphorin 6A, a transmembrane protein previously implicated as a receptor that signals axon repulsion, and the Eph4a receptor tyrosine kinase. The authors suggest that this method will contribute to the creation of a "molecular map of axonal projections" and will deposit the information about PLAP-expressing embryonic stem cells and transgenic mouse lines in an online database (

P. A. Leighton, K. J. Mitchell, L. V. Goodrich, X. Lu, K. Pinson, P. Scherz, W. C. Skarnes, M. Tessier-Lavigne. Defining brain wiring patterns and mechanisms through gene trapping in mice. Nature 410, 174-179 (2001). [Online Journal]