scholarly journals Extracellular matrix-associated molecules collaborate with ciliary neurotrophic factor to induce type-2 astrocyte development.

1990 ◽  
Vol 111 (2) ◽  
pp. 635-644 ◽  
Author(s):  
L E Lillien ◽  
M Sendtner ◽  
M C Raff
Keyword(s):  
Extracellular Matrix ◽  
Progenitor Cells ◽  
Neurotrophic Factor ◽  
Ciliary Neurotrophic Factor ◽  
Oligodendrocyte Differentiation ◽  
Stable Type ◽  
Extracellular Signals ◽  
Astrocyte Differentiation

O-2A progenitor cells give rise to both oligodendrocytes and type-2 astrocytes in vitro. Whereas oligodendrocyte differentiation occurs constitutively, type-2 astrocyte differentiation requires extracellular signals, one of which is thought to be ciliary neurotrophic factor (CNTF). CNTF, however, is insufficient by itself to induce the development of stable type-2 astrocytes. In this report we show the following: (a) that molecules associated with the extracellular matrix (ECM) cooperate with CNTF to induce stable type-2 astrocyte differentiation in serum-free cultures. The combination of CNTF and the ECM-associated molecules thus mimics the effect of FCS, which has been shown previously to induce stable type-2 astrocyte differentiation in vitro. (b) Both the ECM-associated molecules and CNTF act directly on O-2A progenitor cells and can induce them to differentiate prematurely into type-2 astrocytes. (c) ECM-associated molecules also inhibit oligodendrocyte differentiation, even in the absence of CNTF, but this inhibition is not sufficient on its own to induce type-2 astrocyte differentiation. (d) Whereas the effect of ECM on oligodendrocyte differentiation is mimicked by basic fibroblast growth factor (bFGF), the effect of ECM on type-2 astrocyte differentiation is not. (e) The ECM-associated molecules that are responsible for inhibiting oligodendrocyte differentiation and for cooperating with CNTF to induce type-2 astrocyte differentiation are made by non-glial cells in vitro. (f) Molecules that have these activities and bind to ECM are present in the optic nerve at the time type-2 astrocytes are thought to be developing.

scholarly journals Ciliary neurotrophic factor and leukemia inhibitory factor promote the generation, maturation and survival of oligodendrocytes in vitro

Development ◽  
1994 ◽  
Vol 120 (1) ◽  
pp. 143-153 ◽  
Author(s):  
M. Mayer ◽  
K. Bhakoo ◽  
M. Noble
Keyword(s):  
Extracellular Matrix ◽  
Leukemia Inhibitory Factor ◽  
Basic Protein ◽  
Ciliary Neurotrophic Factor ◽  
Alternative Pathways ◽  
Astrocyte Differentiation ◽  
Per Se ◽  
Extracellular Environment

We have found that CNTF and LIF are pleiotropic modulators of development in the O-2A lineage. Both molecules enhanced the generation of oligodendrocytes in cultures of dividing O-2A progenitors. CNTF and LIF also promoted oligodendrocyte maturation, as determined by expression of myelin basic protein, and could promote oligodendrocyte survival to an extent comparable with insulin-like growth factor-1 or insulin. In addition, LIF and CNTF both promoted the differentiation of O-2A progenitors into type-2 astrocytes but only when applied in the presence of extracellular matrix (EnMx) derived from cultures of endothelial cells. The ability of CNTF and LIF to enhance differentiation of O-2A progenitors along either of the alternative pathways of oligodendrocyte and astrocyte differentiation suggests that these proteins are able to enhance the process of differentiation per se, while the actual path of differentiation promoted is determined by the presence or absence of additional molecules in the extracellular environment.

PDGF receptors on cells of the oligodendrocyte-type-2 astrocyte (O-2A) cell lineage

Development ◽  
1989 ◽  
Vol 105 (3) ◽  
pp. 595-603 ◽  
Author(s):  
I.K. Hart ◽  
W.D. Richardson ◽  
C.H. Heldin ◽  
B. Westermark ◽  
M.C. Raff
Keyword(s):  
Progenitor Cells ◽  
Progenitor Cell ◽  
Human Fibroblasts ◽  
Cell Lineage ◽  
Pdgf Receptor ◽  
Oligodendrocyte Differentiation ◽  
Oligodendrocyte Development

It has been shown previously that cultures of rat optic nerve contain three types of macroglial cells—oligodendrocytes and two types of astrocytes. Type-1 astrocytes develop from their own precursor cells beginning before birth, while oligodendrocytes and type-2 astrocytes develop postnatally from a common bipotential precursor called the O-2A progenitor cell. Proliferating O-2A progenitor cells give rise to postmitotic oligodendrocytes beginning around birth, and to type-2 astrocytes beginning in the second postnatal week. Studies in vitro have suggested that platelet-derived growth factor (PDGF), secreted by type-1 astrocytes, plays an important part in timing oligodendrocyte development: PDGF seems to keep O-2A progenitor cells proliferating until an intrinsic clock in the progenitor cells initiates the process leading to oligodendrocyte differentiation. The clock apparently determines when a progenitor cell becomes unresponsive to PDGF, at which point the cell stops dividing and, as a consequence, automatically differentiates into an oligodendrocyte. Here we have used radiolabelled PDGF to show that O-2A progenitor cells have PDGF receptors, suggesting that these cells respond directly to PDGF. The receptors resemble the type A PDGF receptor previously described on human fibroblasts and are initially retained when progenitor cells stop dividing and develop in vitro into oligodendrocytes. The latter finding indicates that receptor loss is not the reason that progenitor cells initially become mitotically unresponsive to PDGF.

scholarly journals Dedifferentiation of Adult Human Myoblasts Induced by Ciliary Neurotrophic Factor In Vitro

2005 ◽  
Vol 16 (7) ◽  
pp. 3140-3151 ◽  
Author(s):  
Xiaoping Chen ◽  
Zebin Mao ◽  
Shuhong Liu ◽  
Hong Liu ◽  
Xuan Wang ◽  
...  
Keyword(s):  
Progenitor Cells ◽  
Neurotrophic Factor ◽  
Mapk Pathway ◽  
Specific Inhibitor ◽  
Ciliary Neurotrophic Factor ◽  
Cellular Effects ◽  
Adult Human ◽  
Clonal Level ◽  
Myogenic Lineage

Ciliary neurotrophic factor (CNTF) is primarily known for its important cellular effects within the nervous system. However, recent studies indicate that its receptor can be highly expressed in denervated skeletal muscle. Here, we investigated the direct effect of CNTF on skeletal myoblasts of adult human. Surprisingly, we found that CNTF induced the myogenic lineage-committed myoblasts at a clonal level to dedifferentiate into multipotent progenitor cells—they not only could proliferate for over 20 passages with the expression absence of myogenic specific factors Myf5 and MyoD, but they were also capable of differentiating into new phenotypes, mainly neurons, glial cells, smooth muscle cells, and adipocytes. These “progenitor cells” retained their myogenic memory and were capable of redifferentiating into myotubes. Furthermore, CNTF could activate the p44/p42 MAPK and down-regulate the expression of myogenic regulatory factors (MRFs). Finally, PD98059, a specific inhibitor of p44/p42 MAPK pathway, was able to abolish the effects of CNTF on both myoblast fate and MRF expression. Our results demonstrate the myogenic lineage-committed human myoblasts can dedifferentiate at a clonal level and CNTF is a novel regulator of skeletal myoblast dedifferentiation via p44/p42 MAPK pathway.

scholarly journals Ciliary neurotrophic factor induces type-2 astrocyte differentiation in culture

Nature ◽  
1988 ◽  
Vol 335 (6185) ◽  
pp. 70-73 ◽  
Author(s):  
Simon M. Hughes ◽  
Laura E. Lillien ◽  
Martin C. Raff ◽  
Hermann Rohrer ◽  
Michael Sendtner
Keyword(s):  
Neurotrophic Factor ◽  
Ciliary Neurotrophic Factor ◽  
Astrocyte Differentiation

Ciliary Neurotrophic Factor Enhances the Survival of Purkinje Cells In Vitro

1994 ◽  
Vol 6 (6) ◽  
pp. 1015-1025 ◽  
Author(s):  
Lena Lärkfors ◽  
Ronald M. Lindsay ◽  
Ralph F. Alderson
Keyword(s):  
Purkinje Cells ◽  
Neurotrophic Factor ◽  
Ciliary Neurotrophic Factor

scholarly journals Ciliary neurotrophic factor induces cholinergic differentiation of rat sympathetic neurons in culture.

1989 ◽  
Vol 108 (5) ◽  
pp. 1807-1816 ◽  
Author(s):  
S Saadat ◽  
M Sendtner ◽  
H Rohrer
Keyword(s):  
Neurotrophic Factor ◽  
Specific Activity ◽  
Sympathetic Neurons ◽  
Ciliary Neurotrophic Factor ◽  
Activity Levels ◽  
Term Survival ◽  
Selective Survival ◽  
Enzyme Molecules

Ciliary neurotrophic factor (CNTF) influences the levels of choline acetyltransferase (ChAT) and tyrosine hydroxylase (TH) in cultures of dissociated sympathetic neurons from newborn rats. In the presence of CNTF both the total and specific activity of ChAT was increased 7 d after culture by 15- and 18-fold, respectively, as compared to cultures kept in the absence of CNTF. Between 3 and 21 d in culture in the presence of CNTF the total ChAT activity increased by a factor of greater than 100. Immunotitration demonstrated that the elevated ChAT levels were due to an increased number of enzyme molecules. In contrast to the increase in ChAT levels, the total and specific activity levels of TH were decreased by 42 and 36%, respectively, after 7 d in culture. Half-maximal effects for both ChAT increase and TH decrease were obtained at CNTF concentrations of approximately 0.6 ng and maximal levels were reached at 1 ng of CNTF per milliliter of medium. The effect of CNTF on TH and ChAT levels were seen in serum-containing medium as well as in serum-free medium. CNTF was shown to have only a small effect on the long-term survival of rat sympathetic neurons. We therefore concluded that the effects of CNTF on ChAT and TH are not due to selective survival of cells that acquire cholinergic traits in vitro, but are rather due to the induction of cholinergic differentiation of noradrenergic sympathetic neurons.

Ciliary neurotrophic factor blocks rod photoreceptor differentiation from postmitotic precursor cells in vitro

1998 ◽  
Vol 291 (2) ◽  
pp. 207-216 ◽  
Author(s):  
Matthias Kirsch ◽  
Steffen Schulz-Key ◽  
Annette Wiese ◽  
Sabine Fuhrmann ◽  
H.-D. Hofmann
Keyword(s):  
Neurotrophic Factor ◽  
Ciliary Neurotrophic Factor ◽  
Precursor Cells ◽  
Rod Photoreceptor
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