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The Journal of Neuroscience, April 4, 2007, 27(14):3921-3932; doi:10.1523/JNEUROSCI.4710-06.2007

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Development/Plasticity/Repair
Plexin-B2 Controls the Development of Cerebellar Granule Cells

Roland H. Friedel,^1 * Géraldine Kerjan,^2 * Helen Rayburn,¹ Ulrich Schüller,³ Constantino Sotelo,^2,4 Marc Tessier-Lavigne,¹ and Alain Chédotal²

¹Department of Biological Sciences, Howard Hughes Medical Institute, Stanford University, Stanford, California 94305, ²Centre National de la Recherche Scientifique, Unité Mixte de Recherche 7102, Université Paris 6, 75005 Paris, France, ³Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts 02115, and ⁴Cátedra de Neurobiología del Desarrollo "Remedios Caro Almela," Instituto de Neurociencias de Alicante, Universidad Miguel Hernández de Elche, Consejo Superior de Investigaciones Científicas, 03550 San Juan de Alicante, Alicante, Spain

Correspondence should be addressed to either of the following: Dr. Alain Chédotal, Centre National de la Recherche Scientifique, Unité Mixte de Recherche 7102, Université Paris 6, 9 Quai Saint Bernard, 75005 Paris, France, Email: alain.chedotal{at}snv.jussieu.fr; or Dr. Marc Tessier-Lavigne, Genentech Inc., 1 DNA Way, South San Francisco, CA 94080, Email: marctl{at}gene.com

Cerebellar granule cell progenitors proliferate postnatally in the upper part of the external granule cell layer (EGL) of the cerebellum. Postmitotic granule cells differentiate and migrate, tangentially in the EGL and then radially through the molecular and Purkinje cell layers. The molecular control of the transition between proliferation and differentiation in cerebellar granule cells is poorly understood. We show here that the transmembrane receptor Plexin-B2 is expressed by proliferating granule cell progenitors. To study Plexin-B2 function, we generated a targeted mutation of mouse Plexin-B2. Most Plexin-B2^–/– mutants die at birth as a result of neural tube closure defects. Some mutants survive but their cerebellum cytoarchitecture is profoundly altered. This is correlated with a disorganization of the timing of granule cell proliferation and differentiation in the EGL. Many differentiated granule cells migrate inside the cerebellum and keep proliferating. These results reveal that Plexin-B2 controls the balance between proliferation and differentiation in granule cells.

Key words: cerebellum; granule cell; semaphorin; cell proliferation; plexin; migration

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Received Oct. 30, 2006; revised Feb. 20, 2007; accepted Feb. 27, 2007.

Correspondence should be addressed to either of the following: Dr. Alain Chédotal, Centre National de la Recherche Scientifique, Unité Mixte de Recherche 7102, Université Paris 6, 9 Quai Saint Bernard, 75005 Paris, France, Email: alain.chedotal{at}snv.jussieu.fr; or Dr. Marc Tessier-Lavigne, Genentech Inc., 1 DNA Way, South San Francisco, CA 94080, Email: marctl{at}gene.com

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