Neurogenesis in the mammalian central nervous system is believed to end in the period just after birth; in the mouse striatum no new neurons are produced after the first few days after birth. In this study, cells isolated from the striatum of the adult mouse brain were induced to proliferate in vitro by epidermal growth factor. The proliferating cells initially expressed nestin, an intermediate filament found in neuroepithelial stem cells, and subsequently developed the morphology and antigenic properties of neurons and astrocytes. Newly generated cells with neuronal morphology were immunoreactive for gamma-aminobutyric acid and substance P, two neurotransmitters of the adult striatum in vivo. Thus, cells of the adult mouse striatum have the capacity to divide and differentiate into neurons and astrocytes.

https://science.sciencemag.org/content/sci/255/5052/1707.full.pdf

Generation of neurons and astrocytes from isolated cells of the adult mammalian central nervous system

The mitogenic actions of epidermal growth factor (EGF) were examined in low-density, dissociated cultures of embryonic day 14 mouse striatal primordia, under serum-free defined conditions. EGF induced the proliferation of single progenitor cells that began to divide between 5 and 7 d in vitro, and after 13 d in vitro had formed a cluster of undifferentiated cells that expressed nestin, an intermediate filament present in neuroepithelial stem cells. In the continued presence of EGF, cells migrated from the proliferating core and differentiated into neurons and astrocytes. The actions of EGF were mimicked by the homolog transforming growth factor alpha (TGF alpha), but not by NGF, basic fibroblast growth factor, platelet-derived growth factor, or TGF beta. In EGF-generated cultures, cells with neuronal morphology contained immunoreactivity for GABA, substance P, and methionine-enkephalin, three neurotransmitters of the adult striatum. Amplification of embryonic day 14 striatal mRNA by using reverse transcription/PCR revealed mRNAs for EGF, TGF alpha, and the EGF receptor. These findings suggest that EGF and/or TGF alpha may act on a multipotent progenitor cell in the striatum to generate both neurons and astrocytes.

https://www.jneurosci.org/content/jneuro/12/11/4565.full.pdf

A multipotent EGF-responsive striatal embryonic progenitor cell produces neurons and astrocytes.

Distinct neural stem cells proliferate in response to EGF and FGF in the developing mouse telencephalon.

Philosophers defined the eye as a window to the soul long before scientists addressed this cliche to determine its scientific basis and clinical relevance. Anatomically and developmentally, the retina is known as an extension of the CNS; it consists of retinal ganglion cells, the axons of which form the optic nerve, whose fibres are, in effect, CNS axons. The eye has unique physical structures and a local array of surface molecules and cytokines, and is host to specialized immune responses similar to those in the brain and spinal cord. Several well-defined neurodegenerative conditions that affect the brain and spinal cord have manifestations in the eye, and ocular symptoms often precede conventional diagnosis of such CNS disorders. Furthermore, various eye-specific pathologies share characteristics of other CNS pathologies. In this Review, we summarize data that support examination of the eye as a noninvasive approach to the diagnosis of select CNS diseases, and the use of the eye as a valuable model to study the CNS. Translation of eye research to CNS disease, and deciphering the role of immune cells in these two systems, could improve our understanding and, potentially, the treatment of neurodegenerative disorders.

The retina as a window to the brain-from eye research to CNS disorders.

bFGF regulates the proliferative fate of unipotent (neuronal) and bipotent (neuronal/astroglial) EGF-generated CNS progenitor cells

EGF and TGF-α stimulate retinal neuroepithelial cell proliferation in vitro

Recent data indicate that the process of neurogenesis in the mammalian central nervous system (CNS) may be regulated by peptide growth factors, such as epidermal growth factor, transforming growth factor-alpha, and acidic or basic fibroblast growth factor. We have investigated whether members of the transforming growth factor-beta (TGFβ) family also play a role in this process and have found that TGFβ-3 is mitogenic for embryonic rat retinal cells in vitro. We also show that TGFβ-3 stimulates production of retinal amacrine cells while photoreceptor production remains unchanged. These data demonstrate that TGFβ-3 can regulate cell proliferation in the CNS during development and can also influence commitment or differentiation, or both, of neural progenitor cells to particular retinal fates. © 1995 John Wiley & Sons, Inc.

Raymond M. Anchan

Papers

EGF and TGF-α stimulate retinal neuroepithelial cell proliferation in vitro

Transforming growth factor-beta-3 is mitogenic for rat retinal progenitor cells in vitro.