GLI3 Is Required for OLIG2+ Progeny Production in Adult Dorsal Neural Stem Cells.

Rebecca J Embalabala,Amanda R Jurewicz,Asa A Brockman,Kaitlyn Ryan,Jennifer A Kong,Chin Chiang,Rebecca A Ihrie,Cristina D Guinto,Arturo Álvarez-Buylla

doi:10.3390/cells11020218

Abstract

The ventricular–subventricular zone (V-SVZ) is a postnatal germinal niche. It holds a large population of neural stem cells (NSCs) that generate neurons and oligodendrocytes for the olfactory bulb and (primarily) the corpus callosum, respectively. These NSCs are heterogeneous and generate different types of neurons depending on their location. Positional identity among NSCs is thought to be controlled in part by intrinsic pathways. However, extrinsic cell signaling through the secreted ligand Sonic hedgehog (Shh) is essential for neurogenesis in both the dorsal and ventral V-SVZ. Here we used a genetic approach to investigate the role of the transcription factors GLI2 and GLI3 in the proliferation and cell fate of dorsal and ventral V-SVZ NSCs. We find that while GLI3 is expressed in stem cell cultures from both dorsal and ventral V-SVZ, the repressor form of GLI3 is more abundant in dorsal V-SVZ. Despite this high dorsal expression and the requirement for other Shh pathway members, GLI3 loss affects the generation of ventrally-, but not dorsally-derived olfactory interneurons in vivo and does not affect trilineage differentiation in vitro. However, loss of GLI3 in the adult dorsal V-SVZ in vivo results in decreased numbers of OLIG2-expressing progeny, indicating a role in gliogenesis.

Highlights

We find that interneuron subtype formation in the olfactory bulb is not altered when GLI3 is ablated singly or in concert with GLI2, effects on total numbers of interneurons are seen in the ventral subregion, and that loss of GLI3 in cultured perinatal neural progenitors from either region does not affect production of neurons or glia
While previous studies have indicated that Gli3 transcript is present in both dorsal and ventral V-SVZ [16], the relative levels of repressor and full-length forms of the protein have not been reported
How and when positional identity is first encoded in the cells of the V-SVZ remains an active area of investigation, as well as the mechanisms that lead to neuronal and glial lineage generation in different subdomains throughout life

Summary

Introduction

The ventricular–subventricular zone (V-SVZ) is a postnatal germinal niche. It holds a large population of neural stem cells (NSCs) that generate neurons and oligodendrocytes for the olfactory bulb and (primarily) the corpus callosum, respectively. GLI3 is expressed in stem cell cultures from both dorsal and ventral V-SVZ, the repressor form of GLI3 is more abundant in dorsal V-SVZ. Despite this high dorsal expression and the requirement for other Shh pathway members, GLI3 loss affects the generation of ventrally-, but not dorsally-derived olfactory interneurons in vivo and does not affect trilineage differentiation in vitro.

Methods

Results

Conclusion