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Neuron-glial Interaction in the Developing Peripheral Nervous System
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Developmental Genetics.
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.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 697
Keyword [en]
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
Neurosciences
Research subject
Neuroscience
Identifiers
URN: urn:nbn:se:uu:diva-157968ISBN: 978-91-554-8142-1 (print)OAI: oai:DiVA.org:uu-157968DiVA: diva2:438068
Public defence
2011-10-14, B22, BMC, Husargatan 3, Uppsala, 13:00 (English)
Opponent
Supervisors
Available from: 2011-09-22 Created: 2011-08-28 Last updated: 2018-01-12Bibliographically approved
List of papers
1. Environmental cues from CNS, PNS, and ENS cells regulate CNS progenitor differentiation
Open this publication in new window or tab >>Environmental cues from CNS, PNS, and ENS cells regulate CNS progenitor differentiation
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.

Keyword
cerebellum, coculture, dorsal root ganglion, multipotency, neural stem/progenitor cells, intestine
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-98176 (URN)10.1097/WNR.0b013e32830bfba4 (DOI)000258767700007 ()18695508 (PubMedID)
Available from: 2009-02-16 Created: 2009-02-16 Last updated: 2017-12-13Bibliographically approved
2. Spatiotemporal Distribution and Function of N-Cadherin in Postnatal Schwann Cells: A Matter of Adhesion?
Open this publication in new window or tab >>Spatiotemporal Distribution and Function of N-Cadherin in Postnatal Schwann Cells: A Matter of Adhesion?
Show others...
2010 (English)In: Journal of Neuroscience Research, ISSN 0360-4012, E-ISSN 1097-4547, Vol. 88, no 11, 2338-2349 p.Article in journal (Refereed) Published
Abstract [en]

During embryonic development of the peripheral nervous system (PNS), the adhesion molecule neuronal cadherin (N-cadherin) is expressed by Schwann cell precursors and associated with axonal growth cones. N-cadherin expression levels decrease as precursors differentiate into Schwann cells. In this study, we investigated the distribution of N-cadherin in the developing postnatal and adult rat peripheral nervous system. N-cadherin was found primarily in ensheathing glia throughout development, concentrated at neuron glial or glial glial contacts of the sciatic nerve, dorsal root ganglia (DRG), and myenteric plexi. In the sciatic nerve, N-cadherin decreases with age and progress of myelination. In adult animals, N-cadherin was found exclusively in nonmyelinating Schwann cells. The distribution of N-cadherin in developing E17 DRG primary cultures is similar to what was observed in vivo. Functional studies of N-cadherin in these cultures, using the antagonist peptide INPISGQ, show a disruption of the attachment between Schwann cells, but no interference in the initial or long-term contact between Schwann cells and axons. We suggest that N-cadherin acts primarily in the adhesion between glial cells during postnatal development. It may form adherents/junctions between nonmyelinating glia, which contribute to the stable tubular structure encapsulating thin caliber axons and thus stabilize the nerve structure as a whole.

Keyword
PNS development, nonmyelinating Schwann cells, myelination, enteric glia, satellite cells
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-135742 (URN)10.1002/jnr.22398 (DOI)000280436600004 ()20623533 (PubMedID)
Available from: 2010-12-08 Created: 2010-12-08 Last updated: 2017-12-11Bibliographically approved
3. The function of GABA and its B-receptor in Schwann cell development
Open this publication in new window or tab >>The function of GABA and its B-receptor in Schwann cell development
Show others...
(English)Manuscript (preprint) (Other academic)
Keyword
GABA, GABA(B) receptor, GAD, Schwann cell, nonmyelinating Schwann cell, satellite cell, baclofen, CGP55485
National Category
Neurosciences
Research subject
Neuroscience
Identifiers
urn:nbn:se:uu:diva-157967 (URN)
Available from: 2011-08-28 Created: 2011-08-28 Last updated: 2018-01-12

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