Optimal Extracellular Matrix Niches for Neurogenesis: Identifying Glycosaminoglycan Chain Composition in the Subventricular Neurogenic Zone

In the adult mammalian brain, new neurons are generated in a restricted region called the neurogenic niche, which refers to the specific regulatory microenvironment of neural stem cells (NSCs). Among the constituents of neurogenic niches, the extracellular matrix (ECM) has emerged as a key player in NSC maintenance, proliferation, and differentiation. In particular, heparan sulfate (HS) proteoglycans are capable of regulating various growth factor signaling pathways that influence neurogenesis. In this review, we summarize our current understanding of the ECM niche in the adult subventricular zone (SVZ), with a special focus on basement membrane (BM)-like structures called fractones, and discuss how fractones, particularly their composition of glycosaminoglycans (GAGs), may influence neurogenesis.

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Brain micro-ecologies: neural stem cell niches in the adult mammalian brain

Philosophical Transactions of the Royal Society B Biological Sciences ◽

10.1098/rstb.2006.2016 ◽

2007 ◽

Vol 363 (1489) ◽

pp. 123-137 ◽

Cited By ~ 172

Author(s):

Patricio A Riquelme ◽

Elodie Drapeau ◽

Fiona Doetsch

Keyword(s):

Stem Cell ◽

Cell Fate ◽

Neural Stem Cell ◽

Subventricular Zone ◽

Hippocampal Formation ◽

Mammalian Brain ◽

Adult Neural Stem Cell ◽

Stem Cell Fate ◽

Stem Cell Niches ◽

Adult Mammalian Brain

Neurogenesis persists in two germinal regions in the adult mammalian brain, the subventricular zone of the lateral ventricles and the subgranular zone in the hippocampal formation. Within these two neurogenic niches, specialized astrocytes are neural stem cells, capable of self-renewing and generating neurons and glia. Cues within the niche, from cell–cell interactions to diffusible factors, are spatially and temporally coordinated to regulate proliferation and neurogenesis, ultimately affecting stem cell fate choices. Here, we review the components of adult neural stem cell niches and how they act to regulate neurogenesis in these regions.

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Subventricular Zone-Mediated Ependyma Repair in the Adult Mammalian Brain

Journal of Neuroscience ◽

10.1523/jneurosci.0224-08.2008 ◽

2008 ◽

Vol 28 (14) ◽

pp. 3804-3813 ◽

Cited By ~ 73

Author(s):

J. Luo ◽

B. A. Shook ◽

S. B. Daniels ◽

J. C. Conover

Keyword(s):

Subventricular Zone ◽

Mammalian Brain ◽

Adult Mammalian Brain

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Gpnmb inhibits oligodendrocyte differentiation of adult neural stem cells by amplifying TGFβ1 signaling

10.1101/2021.08.13.456269 ◽

2021 ◽

Author(s):

Daniel Z Radecki ◽

Albert R Wang ◽

Abigail S Johnson ◽

Christian A Overman ◽

Madison M Thatcher ◽

...

Keyword(s):

Stem Cells ◽

Neural Stem Cells ◽

Signaling Pathway ◽

Subventricular Zone ◽

Mammalian Brain ◽

Receptor Subunit ◽

Oligodendrocyte Differentiation ◽

Feed Forward Loop ◽

Adult Mammalian Brain ◽

Sustained Activation

Gli1 expressing neural stem cells, in the subventricular zone of the adult mammalian brain, respond to demyelination injury by differentiating into oligodendrocytes. We have identified Gpnmb as a novel regulator of oligodendrogenesis in Gli1 neural stem cells, whose expression is induced by TGFβ1 signaling via Gli1, in response to a demyelinating injury. Upregulation of Gpnmb further activates the TGFβ1 pathway by increasing the expression of the TGFβ1 binding receptor subunit, TGFβR2. Thus the TGFβ1→Gli1→Gpnmb→TGFβR2 signaling pathway forms a feed forward loop for sustained activation of TGFβ1 signaling in Gli1 neural stem cells, resulting in inhibition of their differentiation into mature oligodendrocytes following demyelination.

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Improving Neurorepair in Stroke Brain Through Endogenous Neurogenesis-Enhancing Drugs

Cell Transplantation ◽

10.1177/0963689717721230 ◽

2017 ◽

Vol 26 (9) ◽

pp. 1596-1600 ◽

Cited By ~ 13

Author(s):

Kuo-Jen Wu ◽

Seongjin Yu ◽

Jea-Young Lee ◽

Barry Hoffer ◽

Yun Wang

Keyword(s):

Cell Death ◽

Subventricular Zone ◽

De Novo ◽

Neural Regeneration ◽

Mammalian Brain ◽

Stroke Therapy ◽

Pharmacological Manipulation ◽

General Status ◽

Adult Mammalian Brain

Stroke induces not only cell death but also neurorepair. De novo neurogenesis has been found in the subventricular zone of the adult mammalian brain days after stroke. Most of these newly generated cells die shortly after the insult. Recent studies have shown that pharmacological manipulation can improve the survival of endogenous neuroprogenitor cells and neural regeneration in stroke rats. As these drugs target the endogenous reparative processes that occur days after stroke, they may provide a prolonged window for stroke therapy. Here, we discuss endogenous neurogenesis-enhancing drugs and review the general status of stroke therapeutics in evaluating the field of pharmacotherapy for stroke.

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To Become or Not to Become Tumorigenic: Subventricular Zone Versus Hippocampal Neural Stem Cells

Frontiers in Oncology ◽

10.3389/fonc.2020.602217 ◽

2020 ◽

Vol 10 ◽

Author(s):

Ángela Fontán-Lozano ◽

Sara Morcuende ◽

Mª América Davis-López de Carrizosa ◽

Beatriz Benítez-Temiño ◽

Rebeca Mejías ◽

...

Keyword(s):

Stem Cells ◽

Neural Stem Cells ◽

Subventricular Zone ◽

Driver Mutations ◽

Mammalian Brain ◽

Cell Type ◽

Cancer Driver ◽

Zone Versus ◽

Tumor Studies ◽

Adult Mammalian Brain

Neural stem cells (NSCs) persist in the adult mammalian brain in two neurogenic regions: the subventricular zone lining the lateral ventricles and the dentate gyrus of the hippocampus. Compelling evidence suggests that NSCs of the subventricular zone could be the cell type of origin of glioblastoma, the most devastating brain tumor. Studies in glioblastoma patients revealed that NSCs of the tumor-free subventricular zone, harbor cancer-driver mutations that were found in the tumor cells but were not present in normal cortical tissue. Endogenous mutagenesis can also take place in hippocampal NSCs. However, to date, no conclusive studies have linked hippocampal mutations with glioblastoma development. In addition, glioblastoma cells often invade or are closely located to the subventricular zone, whereas they do not tend to infiltrate into the hippocampus. In this review we will analyze possible causes by which subventricular zone NSCs might be more susceptible to malignant transformation than their hippocampal counterparts. Cellular and molecular differences between the two neurogenic niches, as well as genotypic and phenotypic characteristics of their respective NSCs will be discussed regarding why the cell type originating glioblastoma brain tumors has been linked mainly to subventricular zone, but not to hippocampal NSCs.

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