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Midbrain expression of Delta-like 1 homologue is regulated by GDNF and is associated with dopaminergic differentiation.

Christophersen, Nicolaj LU ; Gronborg, Mette; Petersen, Thomas N; Fjord-Larsen, Lone; Jorgensen, Jesper R; Juliusson, Bengt; Blom, Nikolaj; Rosenblad, Carl and Brundin, Patrik LU (2007) In Experimental Neurology 204(2). p.791-801
Abstract
Affymetrix GeneChip technology and quantitative real-time PCR (Q-PCR) were used to examine changes in gene expression in the adult murine substantia nigra pars compacta (SNc) following lentiviral glial cell line-derived neurotrophic factor (GDNF) delivery in adult striatum. We identified several genes that were upregulated after GDNF treatment. Among these, the gene encoding the transmembrane protein Delta-like 1 homologue (Dlk1) was upregulated with a greater than 4-fold increase in mRNA encoding this protein. Immunohistochemistry with a Dlk1-specific antibody confirmed the observed upregulation with increased positive staining of cell bodies in the SNc and fibers in the striatum. Analysis of the developmental regulation of Dlk1 in the... (More)
Affymetrix GeneChip technology and quantitative real-time PCR (Q-PCR) were used to examine changes in gene expression in the adult murine substantia nigra pars compacta (SNc) following lentiviral glial cell line-derived neurotrophic factor (GDNF) delivery in adult striatum. We identified several genes that were upregulated after GDNF treatment. Among these, the gene encoding the transmembrane protein Delta-like 1 homologue (Dlk1) was upregulated with a greater than 4-fold increase in mRNA encoding this protein. Immunohistochemistry with a Dlk1-specific antibody confirmed the observed upregulation with increased positive staining of cell bodies in the SNc and fibers in the striatum. Analysis of the developmental regulation of Dlk1 in the murine ventral midbrain showed that the upregulation of Dlk1 mRNA correlated with the generation of tyrosine hydroxylase (TH)-positive neurons. Furthermore, Dlk1 expression was analyzed in MesC2.10 cells, which are derived from embryonic human mesencephalon and capable of undergoing differentiation into dopaminergic neurons. We detected upregulation of Dlk1 mRNA and protein under conditions where MesC2.10 cells differentiate into a dopaminergic phenotype (41.7+/-7.1% Dlk1+ cells). In contrast, control cultures subjected to default differentiation into non-dopaminergic neurons only expressed very few (3.7+/-1.3%) Dlk1-immunopositive cells. The expression of Dlk1 in MesC2.10 cells was specifically upregulated by the addition of GDNF. Thus, our data suggest that Dlk1 expression precedes the appearance of TH in mesencephalic cells and that levels of Dlk1 are regulated by GDNF. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Delta-like 1 homologue, GDNF, Fetal antigen 1, Dopamine, Neural progenitor, Immortalization, Differentiation
in
Experimental Neurology
volume
204
issue
2
pages
791 - 801
publisher
Academic Press
external identifiers
  • wos:000245682900029
  • scopus:33947648975
ISSN
0014-4886
DOI
10.1016/j.expneurol.2007.01.014
language
English
LU publication?
yes
id
b7de3bf5-93b5-4f97-8e30-c2c56aec87f1 (old id 165455)
alternative location
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=17320866&dopt=Abstract
date added to LUP
2007-07-11 11:59:34
date last changed
2017-09-24 03:35:47
@article{b7de3bf5-93b5-4f97-8e30-c2c56aec87f1,
  abstract     = {Affymetrix GeneChip technology and quantitative real-time PCR (Q-PCR) were used to examine changes in gene expression in the adult murine substantia nigra pars compacta (SNc) following lentiviral glial cell line-derived neurotrophic factor (GDNF) delivery in adult striatum. We identified several genes that were upregulated after GDNF treatment. Among these, the gene encoding the transmembrane protein Delta-like 1 homologue (Dlk1) was upregulated with a greater than 4-fold increase in mRNA encoding this protein. Immunohistochemistry with a Dlk1-specific antibody confirmed the observed upregulation with increased positive staining of cell bodies in the SNc and fibers in the striatum. Analysis of the developmental regulation of Dlk1 in the murine ventral midbrain showed that the upregulation of Dlk1 mRNA correlated with the generation of tyrosine hydroxylase (TH)-positive neurons. Furthermore, Dlk1 expression was analyzed in MesC2.10 cells, which are derived from embryonic human mesencephalon and capable of undergoing differentiation into dopaminergic neurons. We detected upregulation of Dlk1 mRNA and protein under conditions where MesC2.10 cells differentiate into a dopaminergic phenotype (41.7+/-7.1% Dlk1+ cells). In contrast, control cultures subjected to default differentiation into non-dopaminergic neurons only expressed very few (3.7+/-1.3%) Dlk1-immunopositive cells. The expression of Dlk1 in MesC2.10 cells was specifically upregulated by the addition of GDNF. Thus, our data suggest that Dlk1 expression precedes the appearance of TH in mesencephalic cells and that levels of Dlk1 are regulated by GDNF.},
  author       = {Christophersen, Nicolaj and Gronborg, Mette and Petersen, Thomas N and Fjord-Larsen, Lone and Jorgensen, Jesper R and Juliusson, Bengt and Blom, Nikolaj and Rosenblad, Carl and Brundin, Patrik},
  issn         = {0014-4886},
  keyword      = {Delta-like 1 homologue,GDNF,Fetal antigen 1,Dopamine,Neural progenitor,Immortalization,Differentiation},
  language     = {eng},
  number       = {2},
  pages        = {791--801},
  publisher    = {Academic Press},
  series       = {Experimental Neurology},
  title        = {Midbrain expression of Delta-like 1 homologue is regulated by GDNF and is associated with dopaminergic differentiation.},
  url          = {http://dx.doi.org/10.1016/j.expneurol.2007.01.014},
  volume       = {204},
  year         = {2007},
}