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Science 16 May 2008:
Vol. 320. no. 5878, pp. 946 - 949
DOI: 10.1126/science.1155244
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Reports

Early Forebrain Wiring: Genetic Dissection Using Conditional Celsr3 Mutant Mice

Libing Zhou,1 Isabelle Bar,2* Younès Achouri,1 Kenneth Campbell,3 Olivier De Backer,2 Jean M. Hebert,4 Kevin Jones,5 Nicoletta Kessaris,6 Catherine Lambert de Rouvroit,2 Dennis O'Leary,7 William D. Richardson,6 Andre M. Goffinet,1 Fadel Tissir1{dagger}

Development of axonal tracts requires interactions between growth cones and the environment. Tracts such as the anterior commissure and internal capsule are defective in mice with null mutation of Celsr3. We generated a conditional Celsr3 allele, allowing regional inactivation. Inactivation in telencephalon, ventral forebrain, or cortex demonstrated essential roles for Celsr3 in neurons that project axons to the anterior commissure and subcerebral targets, as well as in cells that guide axons through the internal capsule. When Celsr3 was inactivated in cortex, subcerebral projections failed to grow, yet corticothalamic axons developed normally, indicating that besides guidepost cells, additional Celsr3-independent cues can assist their progression. These observations provide in vivo evidence that Celsr3-mediated interactions between axons and guidepost cells govern axonal tract formation in mammals.

1 Developmental Neurobiology, Université Catholique de Louvain, 1200 Bruxelles, Belgique.
2 Facultés Universitaires Notre-Dame de la Paix, 5000 Namur, Belgique.
3 Division of Developmental Biology, Children's Hospital Research Foundation, Cincinnati, OH 45229, USA.
4 Albert Einstein College of Medicine, Bronx, NY 10461, USA.
5 University of Colorado, Boulder, CO 80309, USA.
6 University College London, London WC1E 6AE, UK.
7 Salk Institute, La Jolla, CA 92037, USA.

* Present address: Université Libre de Bruxelles, 1050 Bruxelles, Belgique.

{dagger} To whom correspondence should be addressed. E-mail: fadel.tissir{at}uclouvain.be

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