Prox1 Is Required for Granule Cell Maturation and Intermediate Progenitor Maintenance During Brain Neurogenesis

Abstract

The transcription factor Prox1 plays a crucial role in intermediate progenitor maintenance and hippocampal neuron differentiation during adult neurogenesis in the dentate gyrus region of the hippocampus.

Prospero-related homeobox 1 gene (Prox1) is regulated by canonical Wnt signaling and has a stage-specific role in adult hippocampal neurogenesis

“…Taken together, our data suggest that Prox1 is (i) required for proper neuronal differentiation of granule cells, (ii) sufficient to enhance neuronal differentiation of newborn cells in the adult DG, and (iii) not required for granule cell survival after they have fully matured. Thus, our findings confirm and extend the results recently obtained by using a transgenesis-based approach (17).…”

“…Prox1 is a prospero-related homeodomain transcription factor, which is highly expressed in DG granule cells (10,15,16). Prox1 has previously been shown to be important for lens development, lymphangiogenesis, differentiation of certain spinal cord interneurons, and, very recently, in hippocampal granule cell genesis (17)(18)(19)(20). We analyzed the murine Prox1 promoter/enhancer regions for TCF/LEF sites and found two TCF/LEF consensus sites 49 kb and 43 kb upstream of the Prox1 start codon (Fig.…”

“…It has been recently shown that Prox1 is required for granule cell genesis during embryonic and adult neurogenesis in the hippocampus (17). Given the expression pattern of Prox1 in newborn but also fully mature granule cells, we aimed to analyze the functional role of Prox1 in early and late steps of adult neurogenesis.…”

“…S4), suggesting that Prox1 knockdown affects the level of newborn neurons but not the proliferative activity and/or maintenance of hippocampal NSCs at this time point after Prox1 knockdown. However, this may change in a situation in which Prox1 is chronically depleted: Lavado and colleagues found defective maintenance of radial glia-like NSCs 2 mo after Prox1 KO (17).…”

USP9X deletion elevates the density of oligodendrocytes within the postnatal dentate gyrus

“…It should be noted, however, that a decrease in cell death may simply be a reflection of the fact that there are reduced numbers of new-born neurons present in the mutant hippocampus. Finally, the qPCR analysis also confirmed that the expression of Tnc, Fabp7, Hes5 and the dentate granule neuron marker prospero homeobox protein-1 (Prox1) 24 was significantly reduced in the mutant in comparison to the controls (Fig. 1C).…”