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Environmental cues from CNS, PNS, and ENS cells regulate CNS progenitor differentiation
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
2008 (English)In: NeuroReport, ISSN 0959-4965, E-ISSN 1473-558X, Vol. 19, no 13, 1283-9 p.Article in journal (Refereed) Published
Abstract [en]

Cellular origin and environmental cues regulate stem cell fate determination. Neuroepithelial stem cells form the central nervous system (CNS), whereas neural crest stem cells generate the peripheral (PNS) and enteric nervous system (ENS). CNS neural stem/progenitor cell (NSPC) fate determination was investigated in combination with dissociated cultures or conditioned media from CNS, PNS, or ENS. Cells or media from ENS or PNS cultures efficiently promoted NSPC differentiation into neurons, glia, and smooth muscle cells with a similar morphology as the feeder culture. Together with CNS cells or its conditioned medium, NSPC differentiation was partly inhibited and cells remained immature. Here, we demonstrate that secreted factors from the environment can influence CNS progenitor cells to choose a PNS-like cell fate.

Place, publisher, year, edition, pages
2008. Vol. 19, no 13, 1283-9 p.
Keyword [en]
cerebellum, coculture, dorsal root ganglion, multipotency, neural stem/progenitor cells, intestine
National Category
Medical and Health Sciences
URN: urn:nbn:se:uu:diva-98176DOI: 10.1097/WNR.0b013e32830bfba4ISI: 000258767700007PubMedID: 18695508OAI: oai:DiVA.org:uu-98176DiVA: diva2:173543
Available from: 2009-02-16 Created: 2009-02-16 Last updated: 2014-10-03Bibliographically approved
In thesis
1. Neuron-glial Interaction in the Developing Peripheral Nervous System
Open this publication in new window or tab >>Neuron-glial Interaction in the Developing Peripheral Nervous System
2011 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

The nervous system, including the brain, is the most sophisticated organ in the mammalian body. In such a complex network, neuron-glial interaction is essential and controls most developmental processes, such as stem cell fate determination, migration, differentiation, synapse formation, ensheathment and myelination. Many of these events are critical for the developmental process and small errors can lead to growth retardation, malformation or disease. The understanding of the normal progress of nervous system development is fundamental and will help the discovery of new treatments for disease.

This thesis discusses three types of neuron-glia interactions at different developmental stages; neural stem/progenitor cell (NSPC) differentiation, building and maintaining the structure of the sciatic nerve, and myelin formation.

In Paper I we show that NSPCs, based upon their morphology and expression of specific protein markers, have the capacity to differentiate into cells of either the peripheral nervous system (PNS) or enteric nervous system (ENS) when grown with PNS or ENS primary cell cultures, or fed with conditioned medium from these. This indicates that soluble factors secreted from the PNS or ENS cultures are important for stem cell differentiation and fate determination.

The adhesion protein neuronal cadherin (N-cadherin) is implicated in migration, differentiation and nerve outgrowth in the developing PNS. In Paper II N-cadherin was exclusively found in ensheathing glia (nonmyelinating Schwann cells, satellite cells and enteric glia) in contact with each other or with axons. Functional blocking of N-cadherin in dissociated fetal dorsal root ganglia (DRG) cultures led to a decrease in attachment between Schwann cells. N-cadherin-mediated adhesion of nonmyelinating Schwann cells may be important in encapsulating thin calibre axons and provide support to myelinating Schwann cells.

In Paper III the inhibitory gamma aminobutyric acid (GABA) and GABAB receptors were studied in the Schwann cell of the adult sciatic nerve and DRG cultures. GABAB receptors were primarily expressed in nonmyelinating Schwann cells and protein levels decreased during development and myelination. Blocking the GABAB receptor in long-term DRG cultures led to decreased levels of mRNA markers for myelin. These results indicate that the GABA and GABAB receptors may be involved in Schwann cell myelination.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2011. 63 p.
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 697
Schwann cell, nonmyelinating Schwann cell, myelinating Schwann cell, development, proliferation, differentiation, myelin, neural stem cell, central nervous system, peripheral nervous system, enteric nervous system, N-cadherin, GABA, GAD, GABA(B) receptor, baclofen, CGP55485
National Category
Research subject
urn:nbn:se:uu:diva-157968 (URN)978-91-554-8142-1 (ISBN)
Public defence
2011-10-14, B22, BMC, Husargatan 3, Uppsala, 13:00 (English)
Available from: 2011-09-22 Created: 2011-08-28 Last updated: 2011-11-03Bibliographically approved

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Forsberg-Nilsson, Karin
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