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Brain construction goes straight

Pathfinding is fine without L1–L1 binding.

Brains of mice lacking the cell adhesion molecule L1 are a mess. Failures in neural migration, pathfinding, morphogenesis, and fasciculation result in shortages of cells in various regions and aberrant architecture. But now Itoh et al. (page 145) report that homophilic binding of L1 is not necessary for axonal guidance and neuronal migration in the central nervous system (CNS).

L1 was one of the first neural cell adhesion molecules to be discovered, and its binding partners have been proliferating ever since. Many of those binding partners contact several of L1's many domains, making individual contributions difficult to tease apart. Itoh et al., however, succeed in ablating only a subset of L1's binding interactions via a deletion of L1's sixth Ig domain.

The resulting protein does not bind either to itself or to 5ß1 integrin. And yet mice expressing only this variant have brains and spinal cords that look normal. Thus, it seems that L1 homophilic binding, earlier found to mediate neurite outgrowth in vitro, is not needed for this function in the CNS.

When the L1 variant is backcrossed into another mouse strain, the progeny get hydrocephalus. This swelling of the brain results when cerebrospinal fluid is not correctly cleared from the brain ventricles. The link between L1 mutation and hydrocephalus has been noted before, in humans, but its mechanistic basis remains unclear.

William A. Wells

wellsw{at}rockefeller.edu

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Related Article

Brain development in mice lacking L1–L1 homophilic adhesion

Kyoko Itoh, Ling Cheng, Yoshimasa Kamei, Shinji Fushiki, Hiroyuki Kamiguchi, Paul Gutwein, Alexander Stoeck, Bernd Arnold, Peter Altevogt, and Vance Lemmon
J. Cell Biol. 2004 165: 145-154. [Abstract] [Full Text] [PDF]

This Article Full Text (PDF, 742K) PPT slides of all figures Alert me when this article is cited Services Email this article Similar articles in this journal Alert me to new content in the JCB Download to citation manager Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Wells, W. A. Search for Related Content PubMed Articles by Wells, W. A. Related Collections Related Article Social Bookmarking                            What's this?