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The Journal of Neuroscience, May 16, 2007, 27(20):5495-5505; doi:10.1523/JNEUROSCI.1384-07.2007

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Neurobiology of Disease
Prolonged Glial Expression of Sox4 in the CNS Leads to Architectural Cerebellar Defects and Ataxia

Melanie Hoser,¹ Stephan L. Baader,^2,3 Michael R. Bösl,⁴ Alice Ihmer,² Michael Wegner,¹ and Elisabeth Sock¹

¹Institut für Biochemie, Emil-Fischer-Zentrum, Universität Erlangen, 91054 Erlangen, Germany, ²Anatomisches Institut, Universität Bonn, 53115 Bonn, Germany, ³Institut für Anatomie, Universität Jena, 07743 Jena, Germany, and ⁴Max-Planck-Institut für Neurobiologie, 82152 Martinsried, Germany

Correspondence should be addressed to Dr. Michael Wegner, Institut für Biochemie, Universität Erlangen, Fahrstrasse 17, 91054 Erlangen, Germany. Email: m.wegner{at}biochem.uni-erlangen.de

Sox proteins of group C are strongly expressed in the developing nervous system and have been associated with maturation of neurons and glia. Here, we overexpressed the group C protein Sox4 in transgenic mice under the control of the human GFAP promoter. Transgene expression was detected in radial glia and astrocytes throughout the CNS. The transgenic mice were ataxic and exhibited hydrocephaly as well as cerebellar malformations. In the cerebellum, fissures were not formed and neuronal layering was dramatically disturbed. Nevertheless, all neuronal cell types of the cerebellum were present as well as cells with characteristics of early radial glia, astrocytes, and oligodendrocytes. However, radial glia failed to migrate into the position normally taken by Bergmann glia and did not extend radial fibers toward the pial surface. The cerebellar malformations can therefore be explained by the absence of functional Bergmann glia. We conclude that Sox4 expression counteracts differentiation of radial glia and has to be downregulated before full maturation can occur.

Key words: Sry-box; high-mobility group; Sox4; Bergmann glia; astrocyte; cerebellum

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Received Oct. 27, 2006; accepted April 17, 2007.

Correspondence should be addressed to Dr. Michael Wegner, Institut für Biochemie, Universität Erlangen, Fahrstrasse 17, 91054 Erlangen, Germany. Email: m.wegner{at}biochem.uni-erlangen.de

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