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First published online 14 February 2007
doi: 10.1242/dev.000265

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Hippocampus-like corticoneurogenesis induced by two isoforms of the BTB-zinc finger gene Zbtb20 in mice

Molecular Neurobiology Laboratory, Medical Biotechnology Center, University of Southern Denmark, J. B. Winslowsvej 25, DK-5000 Odense C, Denmark.

^* Author for correspondence (e-mail: naajensen{at}health.sdu.dk)

Accepted 5 January 2007

Hippocampus-associated genes that orchestrate the formation of the compact stratum pyramidale are largely unknown. The BTB (broad complex, tramtrack, bric-a-brac)-zinc finger gene Zbtb20 (also known as HOF, Znf288, Zfp288) encodes two protein isoforms, designated Zbtb20^S and Zbtb20^L, which are expressed in newborn pyramidal neurons of the presumptive hippocampus in mice. Here, we have generated transgenic mice with ectopic expression of Zbtb20^S and Zbtb20^L in immature pyramidal neurons differentiated from multipotent non-hippocampal precursors. The subiculum and posterior retrosplenial areas in these mice were transformed into a three-layered hippocampus-like cortex with a compact homogenous pyramidal cell layer. Severe malformations of lamination occur in neocortical areas, which coincide with a deficiency in expression of cortical lamination markers. The alterations in cortical cytoarchitecture result in behavioral abnormalities suggestive of a deficient processing of visual and spatial memory cues in the cerebral cortex of adult Zbtb20 transgenic mice. Overall, our in vivo data suggest that Zbtb20 functions as a molecular switch for a pathway that induces invariant pyramidal neuron morphogenesis and suppression of cell fate transitions in newborn neurons.

Key words: Zbtb20, HOF, Zfp288, Znf288, BTB, Zinc finger, Cerebral cortex, Hippocampus, Development, Pyramidal neuron, Neurogenesis, Lamination, Migration

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