Background: Differentiation of granule cells (GCs) begins from late embryonic stage in the developing dentate gyrus (DG). Migration of the neurogenic stem cells and progenitors in the developing DG makes understanding of the DG morphogenesis difficult. The proliferative area in the developing DG was divided into the three germinal matrices (GMs). However, the stage of the progenitor cells in each GM along the GC differentiation process is not clear. Results: Here, we extensively compared expression of neurogenic transcription factors (TFs) of which sequential expression in the neocortical development and the adult DG neurogenesis was reported. The GC differentiation marked by Prox1 expression takes place from embryonic day 16.5 in the tertiary GM. Although neurogenesis in each GM basically proceeds along the radial axis of the forming GC layer, cells expressing stem cell markers were observed intermingling with NeuroD/Prox1 expressing differentiated cells in the tertiary GM at postnatal day 5, and gradually restricted in the subgranular zone as the development went on. Conclusions: We describe expression pattern of neurogenic TFs during DG development, which suggests conserved sequential expression of TFs in the GC lineage, and spatiotemporal relationships of GC differentiation and DG morphogenesis during embryonic and early postnatal periods.

The hippocampal formation (HF) is a unique structure in the mammalian brain and is subdivided into the dentate gyrus, Ammon's horn, and subiculum by their functions and connectivity in the neuronal circuit. Because behaviors of the neural stem cells, neuronal progenitors, and the differentiating neurons are complex during hippocampal morphogenesis, the differentiation of these subdivisions has not been well understood. In this study, we investigated embryonic and postnatal expression of the proteins Prox1, Math2, and Ctip2, which clearly indicate principal cells of the dentate gyrus (Prox1 positive) and Ammon's horn (Math2 and Ctip2 positive). Expression patterns of Prox1 and Math2 were consistent with previously suggested localization of migratory pathways of the dentate granule cells and hippocampal pyramidal cells. Interestingly, we found intermingling of Prox1-expressing cells and Math2-expressing cells in a cell migratory stream, suggesting previously unknown behaviors of differentiating cells of the HF.

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This work analyzes the action of enacyloxin Ila, an inhibitor of bacterial protein biosynthesis. Enacyloxin IIa [IC50 on poly(Phe) synthesis approximately 70 nM] is shown to affect the interaction between elongation factor (EF) Tu and GTP or GDP; in particular, the dissociation of EF‐Tu‐GTP is strongly retarded, causing the Kd of EF‐ Tu‐GTP to decrease from 500 to 0.7 nM. In its presence, the migration velocity of both GTP‐ and GDP‐bound EF‐Tu on native PAGE is increased. The stimulation of EF‐Tu‐GDP dissociation by EF‐Ts is inhibited. EF‐ Tu‐GTP can still form a stable complex with aminoacyl‐tRNA (aa‐tRNA), but it no longer protects aa‐tRNA against spontaneous deacylation, showing that the EF‐Tu‐GTP orientation with respect to the 3′ end of aa‐tRNA is modified. However, the EF‐Tu‐dependent binding of aa‐tRNA to the ribosomal A‐site is impaired only slightly by the antibiotic and the activity of the peptidyl‐transferase center, as determined by puromycin reactivity, is not affected. In contrast, the C‐terminal incorporation of Phe into poly(Phe)‐tRNA bound to the P‐site is inhibited, an effect that is observed if Phe‐tRNA is bound to the A‐site nonenzymatically as well. Thus, enacyloxin IIa can affect both EF‐Tu and the ribosomal A‐site directly, inducing an anomalous positioning of aa‐tRNA, that inhibits the incorporation of the amino acid into the polypeptide chain. Therefore, it is the first antibiotic found to have a dual specificity targeted to EF‐Tu and the ribosome.