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