Zbtb20 is essential for the specification of CA1 field identity in the developing hippocampus

Abstract

The development of hippocampal circuitry depends on the proper assembly of correctly specified and fully differentiated hippocampal neurons. Little is known about factors that control the hippocampal specification. Here, we show that zinc finger protein Zbtb20 is essential for the specification of hippocampal CA1 field identity. We found that Zbtb20 expression was initially activated in the hippocampal anlage at the onset of corticogenesis, and persisted in immature hippocampal neurons. Targeted deletion of Zbtb20 in mice did not compromise the progenitor proliferation in the hippocampal and adjacent transitional ventricular zone, but led to the transformation of the hippocampal CA1 field into a transitional neocortex-like structure, as evidenced by cytoarchitectural, neuronal migration, and gene expression phenotypes. Correspondingly, the subiculum was ectopically located adjacent to the CA3 in mutant. Although the field identities of the mutant CA3 and dentate gyrus (DG) were largely maintained, their projections were severely impaired. The hippocampus of Zbtb20 null mice was reduced in size, and exhibited increased apoptotic cell death during postnatal development. Our data establish an essential role of Zbtb20 in the specification of CA1 field identity by repressing adjacent transitional neocortex-specific fate determination.cell fate | neocortex | zinc finger transcription factor

Prox1 postmitotically defines dentate gyrus cells by specifying granule cell identity over CA3 pyramidal cell fate in the hippocampus

“…It has been shown that the CA1 domain in the hippocampus requires the determinant Zbtb20 (Nielsen et al, 2007;Xie et al, 2010). This protein is expressed throughout the CA region and the DG but is necessary only for the development of CA1 pyramidal cells.…”

“…The loss of these factors induces massive apoptosis of DG granule cells, whereas CA regions are not seriously affected (Miyata et al, 1999;Arnold et al, 2008;Galichet et al, 2008). The specification of CA1 pyramidal cells requires the zinc-finger protein Zbtb20 (Nielsen et al, 2007;Xie et al, 2010). However, the molecular mechanisms that specify other neuronal lineages during hippocampal development remain elusive.…”

Tumor suppressor Nf2 limits expansion of the neural progenitor pool by inhibiting Yap/Taz transcriptional coactivators

“…We first examined the expression of a series of markers at E14.5, including: Axin2, which is normally expressed at the hem and ventral hippocampal primordium (Diep et al, 2004); Lef1, which is expressed at the ventral hippocampal primordium (Galceran et al, 2000); the DNE marker Prox1 (Lavado and Oliver, 2007); and the hippocampus marker Zbtb20 (Xie et al, 2010). These markers all showed normal expression patterns in Nf2 mutants (Fig.…”

The Zinc Finger Protein ZBTB20 Regulates Transcription of Fructose-1,6-Bisphosphatase 1 and β Cell Function in Mice

“…15 ZBTB20 plays important roles in multiple systems, as suggested by the severe phenotypes in the mice lacking ZBTB20, which mainly include growth retardation, premature death, hypoglycemia, and hippocampal defect. 16,17 The hypoinsulinemic hypoglycemia phenotype is most likely caused by certain unknown defects beyond a feeding problem, because considerable amounts of milk are consistently present in the stomachs of Zbtb20 knockout mice, suggesting that ZBTB20 may be an important player in glucose homeostasis. 16 Given the critical role of pancreatic exocrine and endocrine cells in glucose metabolism, we analyzed expression pattern and biological functions of ZBTB20 in the pancreas.…”