The microenvironment of the embryonic neural stem cell: Lessons from adult niches?

Lathia, Justin D.; Rao, Mahendra S.; Mattson, Mark P.; ffrench‐Constant, Charles

doi:10.1002/dvdy.21319

Cited by 55 publications

(51 citation statements)

References 226 publications

(272 reference statements)

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“…Because the majority of neural NSPCs in the developing human neocortex (APs, bRGCs, and TAPs), in contrast to the majority of mouse BPs, are capable of undergoing self-renewing divisions, ECM interactions may promote the capacity for sustained self-renewal of NSPCs in the hGZs. This notion is consistent with previous observations and concepts (35)(36)(37)(38) and with our previous findings concerning bRGC maintenance in ferrets and its dependence on integrin signaling (23).…”

supporting

confidence: 94%

Transcriptomes of germinal zones of human and mouse fetal neocortex suggest a role of extracellular matrix in progenitor self-renewal

Fietz

Lachmann²,

Brandl

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

292

370

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The expansion of the neocortex during mammalian brain evolution results primarily from an increase in neural progenitor cell divisions in its two principal germinal zones during development, the ventricular zone (VZ) and the subventricular zone (SVZ). Using mRNA sequencing, we analyzed the transcriptomes of fetal human and embryonic mouse VZ, SVZ, and cortical plate. In mouse, the transcriptome of the SVZ was more similar to that of the cortical plate than that of the VZ, whereas in human the opposite was the case, with the inner and outer SVZ being highly related to each other despite their cytoarchitectonic differences. We describe sets of genes that are up-or down-regulated in each germinal zone. These data suggest that cell adhesion and cell-extracellular matrix interactions promote the proliferation and self-renewal of neural progenitors in the developing human neocortex. Notably, relevant extracellular matrix-associated genes include distinct sets of collagens, laminins, proteoglycans, and integrins, along with specific sets of growth factors and morphogens. Our data establish a basis for identifying novel cell-type markers and open up avenues to unravel the molecular basis of neocortex expansion during evolution.cerebral cortex | neural stem cells | neurogenesis N eocortex expansion is a hallmark of mammalian brain evolution. With regard to neuron number, a major cause of this expansion is the increase in the population size of neural stem and progenitor cells (NSPCs) and the number of divisions that each of the various NSPC types undergoes during cortical development (1-4). Two principal classes of these cells can be distinguished based on the location of their mitosis: (i) apical progenitors (APs), which undergo mitosis at the luminal surface of the ventricular zone (VZ); and (ii) basal progenitors (BPs), which undergo mitosis at an abventricular location, typically in the subventricular zone (SVZ) (2, 5, 6). Neurons born from AP and BP cell divisions migrate radially and settle at the basal (pial) side of the developing cortical wall to form the cortical plate (CP).Both APs and BPs comprise several types of NSPCs that differ in key cell biological features (e.g., cell polarity, cell processes, cell-to-cell junctions, nuclear migration) and in the principal modes of cell division (symmetric proliferative vs. asymmetric self-renewing vs. symmetric or asymmetric consumptive) (2, 5-10). APs comprise neuroepithelial cells, which transform into apical radial glial cells (aRGCs) at the onset of neurogenesis (11), and short neural precursors (12). BPs include basal (or outer) radial glial cells (bRGCs), transit amplifying progenitors (TAPs), and intermediate progenitor cells (IPCs) (2, 3, 13).The evolutionary expansion of the neocortex is associated with an increase in the thickness of the SVZ, which develops into two cytoarchitecturally distinct zones, an inner SVZ (ISVZ) and an outer SVZ (OSVZ) (1-4, 14, 15). The evolutionary increase in the SVZ is accompanied by a change in the proportion of BP subtypes. Fo...

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supporting

confidence: 94%

Transcriptomes of germinal zones of human and mouse fetal neocortex suggest a role of extracellular matrix in progenitor self-renewal

Fietz

Lachmann²,

Brandl

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

292

370

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“…There are several niches in the adult brain in which NSCs persist throughout life and can respond to injurious processes [15][16][17][18]. New neurons are continuously generated in the anterior subventricular zone (SVZ) of adult rodents, from which they migrate via the rostral migratory stream to the olfactory bulb [19][20][21][22][23], and in the subgranular zone of the hippocampal dentate gyrus of both adult rodents [24][25][26][27] and humans [6,28].…”

Section: Glial Progenitor Cells In the Adult Central Nervous Systemmentioning

confidence: 99%

Cell Therapy for Multiple Sclerosis

Ben‐Hur

2011

Neurotherapeutics

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The spontaneous recovery observed in the early stages of multiple sclerosis (MS) is substituted with a later progressive course and failure of endogenous processes of repair and remyelination. Although this is the basic rationale for cell therapy, it is not clear yet to what degree the MS brain is amenable for repair and whether cell therapy has an advantage in comparison to other strategies to enhance endogenous remyelination. Central to the promise of stem cell therapy is the therapeutic plasticity, by which neural precursors can replace damaged oligodendrocytes and myelin, and also effectively attenuate the autoimmune process in a local, nonsystemic manner to protect brain cells from further injury, as well as facilitate the intrinsic capacity of the brain for recovery. These fundamental immunomodulatory and neurotrophic properties are shared by stem cells of different sources. By using different routes of delivery, cells may target both affected white matter tracts and the perivascular niche where the trafficking of immune cells occur. It is unclear yet whether the therapeutic properties of transplanted cells are maintained with the duration of time. The application of neural stem cell therapy (derived from fetal brain or from human embryonic stem cells) will be realized once their purification, mass generation, and safety are guaranteed. However, previous clinical experience with bone marrow stromal (mesenchymal) stem cells and the relative easy expansion of autologous cells have opened the way to their experimental application in MS. An initial clinical trial has established the probable safety of their intravenous and intrathecal delivery. Short-term follow-up observed immunomodulatory effects and clinical benefit justifying further clinical trials.

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“…The importance of Eph/ephrin interactions has also been shown in various stem cell niches, including neural, dental and intestinal stem cell compartments [103,104]. More recent studies show their involvement in bone homeostasis and mesenchymal stem cell (MSC) regulation.…”

Section: Eph/ephrin On Bone Remodeling and Formationmentioning

confidence: 98%

“…Ephrin-B1 full knockout mice are prenatally lethal and they have skeletal defects. Studies on disruption of ephrin-B1 on collagen I producing cells result in reduced bone formation and skull defect and studies on ephrin-B1 conditional knockout mice shows defects in osteoblastic mediated bone formation with no increase in osteoclastic bone resorption and this condition results in reduction in bone size and density [101,102].The importance of Eph/ephrin interactions has also been shown in various stem cell niches, including neural, dental and intestinal stem cell compartments [103,104]. More recent studies show their involvement in bone homeostasis and mesenchymal stem cell (MSC) regulation.…”

mentioning

confidence: 99%

Expression and Function of the Eph Receptor Family in Leukemia and Hematopoietic Malignancies: Prospects for Targeted Therapies

Charmsaz

Boyd²

2013

J Leuk

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There has been considerable interest in recent years in the development of therapies, which target Eph receptors or their ephrin ligands. The Eph receptor tyrosine kinases and their membrane bound ephrin ligands are cell surface molecules involved in many biological functions and cell behaviors during embryogenesis and in adult life. However, they are also expressed in an aberrant fashion on many tumors and are re-expressed on normal cells in nonmalignant pathological states. Some of the eph/ephrins including EphA7 and EphA1 protein are thought to function as tumor suppressors in particular cancers. In tumors where Eph/ephrin proteins are expressed at high levels, being expressed on the cell surface these proteins are readily accessible to antibody-mediated therapies several of which are in advanced pre-clinical or early clinical evaluation, including antibodies specific for EphA2, EphA3, and EphB4 which are expressed on many different tumors. We will review the general features of the Eph/ephrin system and discuss the role of this system in normal hematopoiesis before focusing on the role of Eph proteins in leukemia and other hematological malignancies and possible avenues for therapy.of highly conserved tyrosine residues and a PDZ-binding motif. The conserved tyrosine residues have been shown to serve as a docking site for proteins, which mediate downstream ephrin signaling [2,9] Classification, Structure and Binding of Eph/ephrinThe Eph receptors and their membrane bound ephrin ligands represent the largest family of receptor tyrosine kinases (RTK's). The first member, EphA1, was originally termed Eph, as it was first identified in an Erythropoietin-Producing Hepatocellular (Eph Nomenclature committee, 1997) carcinoma cell line [1]. Fourteen members of the Eph family of RTK have been identified in mammals, which are divided into two groups, the EphA and EphB family. This is based on their sequence homology, ligand specificity and structural features. In mammals there are nine members of the EphA subgroup (EphA1-8 and EphA10) and five EphB receptors (EphB1-4 and EphB6) [2,3].Eph receptors are type I transmembrane proteins composed of extracellular region including a ligand binding domain with two distinct ligand-binding interfaces (N terminal β jelly roll domain) determining the ephrin binding, and a cysteine-rich region containing an epidermal growth factor (EGF)-like motif that is involved in receptor dimerization followed by two fibronectin type-III domains [4,5]. The intracellular region comprised of a conserved juxtamembrane domain, a tyrosine kinase domain and a sterile alpha motif (SAM) domain, the latter having a potential role in receptor clustering [6,7]. Most of the Eph receptors, possess a C-terminal PDZ (Postsynaptic density protein, Disc large, Zona occludens tight junction protein) binding motif that is involved in signaling at a sub-cellular level and in the assembly of large molecular complexes [3,5,8] (Figure 1a).The ephrin ligands of Eph receptors are also membrane bound proteins an...

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The microenvironment of the embryonic neural stem cell: Lessons from adult niches?

Cited by 55 publications

References 226 publications

Transcriptomes of germinal zones of human and mouse fetal neocortex suggest a role of extracellular matrix in progenitor self-renewal

Transcriptomes of germinal zones of human and mouse fetal neocortex suggest a role of extracellular matrix in progenitor self-renewal

Cell Therapy for Multiple Sclerosis

Expression and Function of the Eph Receptor Family in Leukemia and Hematopoietic Malignancies: Prospects for Targeted Therapies

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