|
|
Factors |
Location |
| Embryonic niche | Adult niche |
|
| Growth factors | | |
| BDNF (brain derived neurotrophic factor) | Forebrain
(induces proliferation of embryonic NSC) [8] | DG, SVZ
(promotes neurogenesis) [9, 10] |
|
| Cystatin-C | Neocortex
(promotes astrogenesis and suppresses oligodendrogenesis) [11] | DG, blood vessels
(promotes neurogenesis) [12] |
|
| FGF-2 also known as basic FGF (fibroblast growth factor) | Neuroepithelial cells and RGC
(essential for self-renewal and maintaining multipotency) [5, 13] | SVZ, SGZ of DG
(regulation of NSC and progenitor cells) [14] |
|
| IGFs (insulin growth factors) | Choroid plexus epithelium, CSF, striatal primordial, and neocortex
(stimulates survival and proliferation of NSC) [14–18] | CSF, DG, and hypothalamus
(regulation of NSC proliferation) [19, 20] |
|
| EGF (epidermal growth factor) | Striatal primordial
(induces proliferation of NSC) [21, 22] | SVZ
(induces proliferation of the NSC) [23] |
|
| PDGF-A, PDGF-B (platelet derived growth factor-A, platelet derived growth factor-B) | SVZ
(stimulates differentiation into astrocytes and oligodendrocytes) [24, 25] | SVZ
(induces differentiation of the PDGF-responsive progenitors into glia cells) [26] |
|
| PEDF (pigment epithelium derived factor) | ND | SVZ
(promotes stemness of the NSC) [27, 28] |
|
| GDF-11 (growth differentiation factor-11) | Neuroectodermal tissue
(involved in the earlier steps of the neural plate patterning) [29, 30] | ND |
|
| GDF-15 (growth differentiation factor-15) | Hippocampus
(regulates the migration and differentiation of hippocampal precursors by promoting EGFR signaling) [31] | ND |
|
| GDNF (glial cell line derived neurotrophic factor) | Ventral mesencephalon
(neurotrophic factor for NSC at nigrostriatal region) [32] | DG
(promotes astrogliogenesis from NPC) [33, 34] |
|
| TGF-β1 (transforming growth factor-β1) | Neocortex
(regulates differentiation into astrocytes) [35] | SGZ, GCL of the hippocampus, and EC
(promotes stem cell quiescence and the survival of newly generated neurons) |
|
| VEGF (vascular endothelial growth factor) | Ventricular neuroectoderm, RGC, and EC
(angiogenic and mitogenic factor) | SVZ, SGZ of DG, and EC
(stimulates neurogenesis) [36–38] |
|
| CNTF (ciliary neurotrophic factor) | Choroid plexus, VZ, and forebrain germinal zone
(expansion and self-renewal of NSC) [39, 40]
| SVZ, SGZ of the DG
(regulates the balance between NSC self-renewal and the generation of neuronal progenitors) [41, 42] |
|
| LIF (leukemia inhibitory factor) | Choroid plexus and VZ
(expansion and self-renewal of NSC) [39] | SVZ, CA3 of the hippocampus
(self-renewal of NSC and proliferation of oligodendrocyte progenitor cells) [43, 44] |
|
| Hormones | | |
| GH (growth hormone) | Striatal primordial, neocortex
(stimulates survival of the NPC and proliferation and differentiation of cortical cells) [45, 46] | SVZ
(regulates proliferation of NPC) [47, 48] |
|
| Ghrelin | Spinal cord
(induces proliferation of NSC) [49] | SVZ, SGZ of the hippocampus
(regulates proliferation and differentiation of progenitor cells and migration of neuroblasts in the SVZ) [50] |
|
| EPO (erythropoietin) | Ganglionic eminences
(promotes production of neuronal progenitors) [51] | SVZ, SGZ of the hippocampus
(regulates proliferation and differentiation of progenitor cells and the migration of neuroblasts in the SVZ) [51] |
|
| Morphogens | | |
| BMPs (bone morphogenetic proteins) | Dorsal midline of the telencephalon and cortical hem
(develops mouse olfactory system and SVZ and modulates response to EGF) [52–54] | SVZ, hippocampus
(promotes the survival of SVZ-derived neurons and maintenance of the quiescent state of NSC) [55, 56] |
|
| SHH (sonic hedgehog) | Dorsal telencephalon, CSF, pericytes
(dorsoventral patterning, development of cortex and hippocampus) | SVZ and SGZ of DG
(chemotaxis and maintenance of the NSC) [57, 58] |
|
| Wnt | Caudomedial cortex
(expansion of caudomedial cortical progenitor cells) [59] | Hippocampus
(regulator of neurogenesis) [60] |
|
| Notch-1 | Developing telencephalon
(maintenance of the telencephalic NSC) [3, 61] | DG and SVZ
(modulates adult neurogenesis) [62–64] |
|
| FGF-8a, FGF-8b (fibroblast growth factor-8a, fibroblast growth factor-8b) | Mid-hindbrain
(mitogen for NSC) [65] | ND |
|
| Retinoic acid | Choroid plexus, CSF, and ganglionic eminence
(migration of NPC to cerebral cortex and regulation of neuronal differentiation) [66] | Infrapyramidal and suprapyramidal layers of the hippocampus, SGZ, and SVZ
(regulates proliferation of NPC in the SGZ and neuronal differentiation) [66, 67] |
|
| Extracellular matrix components | | |
| HSPG (heparan sulfate proteoglycan) | Neuroepithelial cells
(essential for many of the protein effectors involved in pluripotency and neural differentiation) [68] | SVZ, fractones [69] |
|
| CSPG (chondroitin sulfate proteoglycan) | Neocortex and ganglionic eminence
(essential for mitogens that promote self-renewal and neurogenesis) [70, 71] | SVZ
(essential for mitogens involved in NSC maintenance) [70, 72] |
|
| Heparin | Neocortex
(interaction with growth factors, proliferation of NSC) [73] | DG, SVZ
(essential for mitogens involved in neurogenesis) [74] |
|
| Laminins | Neuroepithelial cells, VZ
(promote formation of properly polarized cortical neuroepithelium) [75] | SVZ, fractones
(enhance NSC proliferation and self-renewal) [69, 76] |
|
| Collagen | Neocortex
(collagen IV regulates corticogenesis by inhibiting cell proliferation and glial cell differentiation and promotes neuronal differentiation) [77] | SVZ, fractones
(collagen I in subependymal layer and the basal lamina of blood vessels) [69] |
|
| Vitronectin | Developing spinal cord
(promotes differentiation into oligodendrocytes) [70] | ND |
|
| Tenascin | Neocortex, RGC, and spinal cord
(tenascin C promotes EGF response of NSC and promotes oligodendrocyte precursor proliferation and astrocytic lineages) [71, 72] | SVZ and olfactory bulb
(tenascin R regulates neurogenesis and radial migration in the olfactory bulb) [78, 79] |
|
| Reelin | Marginal zone of developing cortex
(controls differentiation, migration, and proliferation of NSC) [80, 81] | SGZ, cortex
(regulation of quiescence and migration of NSC and maintenance of cortical architecture) [82, 83] |
|
| Perlecan | Ventral forebrain and neocortex
(maintains the basal lamina and influences the size of ventral and cortical telencephalic structures) [84] | SVZ, fractones
(promotes growth factor activity in the NSC niche) [85] |
|
