Regulation of archicortical arealization by the transcription factor Zbtb20

Abstract

The molecular mechanisms of regionalization of the medial pallium (MP), the anlage of the hippocampus, and transitional (cingulate and retrosplenial) cortices are largely unknown. Previous analyses have outlined an important role of the transcription factor (TF) Zbtb20 for hippocampal CA1 field specification (Nielsen et al. (2007) Development 134:1133-1140; Nielsen et al. (2010) Cereb Cortex 20:1904-1914; Xie et al. (2010) Proc Natl Acad Sci USA 107:6510-6515). Here, we present novel data showing that Zbtb20 exhibits a ventral(high)-to-dorsal(low) gradient of expression in MP progenitors as well as an expression in postmitotic cells at the transitional cortex/neocortex border. Our detailed pattern analysis revealed that in Zbtb20 loss-of-function the molecular borders between neocortical, transitional, and hippocampal fields are progressively shifted ventrally, leading to an ectopic positioning of all dorsal fields into the neighboring ventrally located areas. Thus, in addition to its known importance for the specification of the hippocampal CA1 sector, the graded expression of TF Zbtb20 in ventricular zone of MP appears to translate early positional information for establishment of all developing MP fields. Our data also suggest that the signaling factor Wnt3a is a putative molecular partner of TF Zbtb20 in this patterning process.

Hypermethylation in the ZBTB20 gene is associated with major depressive disorder

“…Conditionally deleting ZBTB20 specifically in mature CA1 pyramidal neurons impairs long-term potentiation and NMDA receptor (NMDAR)-mediated excitatory post-synaptic currents [27]. ZBTB20 is also crucial for the regionalization and volume of the archicortex [28], which plays a role in depression. In mice, mis-expression of ZBTB20 causes the development of a compact homogenous pyramidal cell layer within the hippocampal region, which is linked to behavioural abnormalities [29].…”

Neurodevelopmental disorders associated with dosage imbalance ofZBTB20correlate with the morbidity spectrum of ZBTB20 candidate target genes

“…Sensorimotor gating can be measured via prepulse inhibition of the startle response, and it is regulated by forebrain circuitry, including parts of the basal ganglia 45. Interestingly, Zbtb20 was identified as part of a quantitative trait locus for prepulse inhibition of startle in mice47 and the gene is also expressed in the developing murine basal ganglia 13. As the basal ganglia are implicated in the pathophysiology of Tourette’s syndrome,45 this correlates with the presence of Tourette’s syndrome in patient 1.…”

“…The murine Zbtb20 gene is expressed in the developing murine brain including the amygdala,14 the basal ganglia,13 the cerebellum and the hippocampus,7 areas involved in processing of memory, emotional reactions and motor coordination 7 13 14. The role of Zbtb20 in murine neurodevelopment is not fully understood.…”

“…The murine Zbtb20 gene is also expressed in the developing hippocampus, where it is essential for specification of CA1 pyramidal neurons 9–13 . Zbtb20 is also expressed in areas of the brain involved in emotion and motor coordination including the amygdala, basal ganglia and cerebellum 7 13 14. Since the murine Zbtb20 and human ZBTB20 proteins are 97% identical with similar expression patterns in the developing murine and human hippocampi,6 7 9 we hypothesised that dosage imbalance of ZBTB20 is central to the pathogenesis of the NDD seen in the 3q13.31 microdeletion syndrome through dysregulation of multiple other neuronal target genes.…”

Human Dental Pulp Stem Cells via the NF-κB Pathway

“…Zinc finger and BTB domain-containing 20 (ZBTB20), also termed DPZF, HOF or ZNF288 [7], belongs to a subfamily of zinc finger proteins containing C2H2 Krüppel-type zinc fingers and BTB/POZ domains. It belongs to a class of nuclear DNA-binding transcription factors which are implicated in many developmental processes [8].…”