GFAP-Positive Progenitor Cell Production is Concentrated in Specific Encephalic Regions in Young Adult Mice

Abstract

Previous genetic fate-mapping studies have indicated that embryonic glial fibrillary acidic protein-positive (GFAP) cells are multifunctional progenitor/neural stem cells that can produce astrocytes as well as neurons and oligodendrocytes throughout the adult mouse central nervous system (CNS). However, emerging evidence from recent studies indicates that GFAP cells adopt different cell fates and generate different cell types in different regions. Moreover, the fate of GFAP cells in the young adult mouse CNS is not well understood. In the present study, hGFAP-Cre/R26R transgenic mice were used to investigate the lineage of embryonic GFAP cells in the young adult mouse CNS. At postnatal day 21, we found that GFAP cells mainly generated NeuN neurons in the cerebral cortex (both ventral and dorsal), hippocampus, and cerebellum. Strangely, these cells were negative for the Purkinje cell marker calbindin in the cerebellum and the neuronal marker NeuN in the thalamus. Thus, contrary to previous studies, our genetic fate-mapping revealed that the cell fate of embryonic GFAP cells at the young adult stage is significantly different from that at the adult stage.

Regulation of embryonic and adult neurogenesis by Ars2

“…Overall, Ars2 deletion yielded animals with distinct cerebellar classes: a strong phenotype accompanied with loss of most granule cells and cerebellar complexity, and a weak phenotype with a mild growth defect and, surprisingly, emergence of lobule I. Previous studies have implicated that different strains of hGFAP-Cre exhibit different recombination patterns in the brain (Casper and McCarthy, 2006;Guo et al, 2018). Here, our observations suggest that the same hGFAP-Cre has varied recombination efficiency in different mice.…”

Expression Patterns of Inducible Cre Recombinase Driven by Differential Astrocyte-Specific Promoters in Transgenic Mouse Lines

“…To elucidate the role of astrocytes in vivo, many transgenic mouse lines have been generated to achieve the astrocyte-specific expression of Cre recombinase in order to manipulate the gene functions and/or the activity of astrocytes by using the Cre-loxp system [14]. However, most existing astrocyte Cre lines, such as glial fibrillary acidic protein (GFAP)-Cre, do not meet the requirement of astrocyte-specific expression of Cre recombinase, in part due to the fact that most of the astrocyte promoters used to drive Cre recombinase expression are also expressed by non-astrocytes during early development [15][16][17]. Thus, there is a persistent need to develop new tools to target astrocytes efficiently with high spatial and temporal specificity [18].…”

Functional analysis of the epilepsy gene Pcdh19 using a novel GFP-reporter mouse model

“…GFAP (glial fibrillary acidic protein) is an intermediate filament protein that is expressed during embryogenesis by multipotent neural stem cells that give rise to neurons and astrocytes in the hippocampus (Guo, Su, and Lou 2018). We used the previously characterized Gfap- Cre line (Gregorian et al 2009) to investigate how specific Pcdh19 elimination in the hippocampus would affect brain physiology.…”