THE ROLE OF ASTROCYTES DURING THE DEVELOPMENT OF THE NEUROGENIC NICHE OF THE DENTATE GYRUS

Adult neurogenesis is highly restricted in the adult mammalian brain. One of the two main regions where it occurs is the subgranular zone (SGZ) of the dentate gyrus (DG) and is attributed to a population of neural stem cells (NSCs) that are in a quiescent state. Through regulated mechanisms, these NSCs are activated (aNSCs) and produce intermediate progenitor cells (IPCs) that generate granule neurons. Neurogenesis and astrogliogenesis occur simultaneously during early postnatal DG development. Astrocytes are key components of the neurogenic niche of the hippocampus, and multiple lines of evidence suggest that they have a significant impact on DG plasticity by positively regulating NSC function. Previous results from our lab have shown that transcription factor Sox5 is expressed in aNSCs and astrocytes in the adult GD and that the loss of Sox5 in those populations does not affect the number or distribution of astrocytes. However, it is unknown if astrocytes might influence the emergence of adult NSC during the development of DG. Using a Nestin-Cre-mediated Sox5 deletion mouse model in NSCs, we have determined that Sox5 is necessary during embryonic/postnatal development to prevent excessive astrogliogenesis. Furthermore, using astrocyte specific inducible Aldh1L1-CreERT2 mediated deletion of Sox5 at postnatal P3, we are analysing the possible astrocyte participation. Our preliminary results confirm that the Aldh1L1-CreERT2 line can drive cre-mediated recombination specifically in astrocytes, with minimal effect on other cell types. Moreover, we can confirm that using Aldh1L1 as a driver results in high recombination efficiency, with most of the recombined cells being astrocytes.