Combinatorial expression of sets of transcriptional regulators along the mammalian cerebral cortex controls its subdivision into functional areas as well as the specification of the various subtypes of cortical projection neurons. Here we show that the transcriptional repressor Zbtb20 is essential for specification of both hippocampal pyramidal neurons and territory in a mouse knockout model. Homozygous Zbtb20-/- mice are viable at birth, but display dwarfism and die during the first month of postnatal life. Characterization of the Zbtb20-/- brain phenotype reveals a small vestigial hippocampus with a dramatic change in the molecular patterning of the subiculum and Ammon’s horn. In absence of Zbtb20, the pattern of expression of distinct molecular markers was altered at four borders: retrosplenial cortex/subiculum, subiculum/CA1, CA1/CA2, and CA2/CA3, leading to a replacement of Ammon’s horn with aberrant transitional midline-like cortex. This pattern defect resulted in a replacement of the densely packed pyramidal neurons of hippocampus proper by aberrantly specified neurons with adjacent transitional cortex-like identities. Together, these findings demonstrate that Zbtb20 functions as an essential regulator of various aspects of neuronal development and corticogenesis in the hippocampus.
Zbtb20, hippocampus, pyramidal neurons, Knockout
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The Brain Prize Meeting 2011 - Neuronal Network Organization and Information Processing