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Neurogenin2 identifies a transplantable dopamine neuron precursor in the developing ventral mesencephalon.

Thompson, Lachlan LU ; Andersson, Elin LU ; Hebsgaard, Josephine LU ; Barraud, Perrine LU ; Guillemot, Francois; Parmar, Malin LU and Björklund, Anders LU (2006) In Experimental Neurology 198(1). p.183-198
Abstract
In neural transplantation studies, there is an interest in identifying and isolating mesencephalic dopamine (mesDA) neuron precursors that have the capacity to differentiate into fully mature mesDA neurons after transplantation. We report here that in the developing ventral mesencephalon (VM) the proneural gene Neurogenin2 (Ngn2) is expressed exclusively in the part of the ventricular zone that gives rise to the migrating mesDA neuroblasts, but not in the differentiated mesDA neurons. From other studies, we know that Ngn2 is involved in the generation of mesDA neurons and that the development of mesDA neurons is severely compromised in Ngn2-null mutant mice. We show here that cells isolated by FACS from the developing VM of Ngn2-GFP... (More)
In neural transplantation studies, there is an interest in identifying and isolating mesencephalic dopamine (mesDA) neuron precursors that have the capacity to differentiate into fully mature mesDA neurons after transplantation. We report here that in the developing ventral mesencephalon (VM) the proneural gene Neurogenin2 (Ngn2) is expressed exclusively in the part of the ventricular zone that gives rise to the migrating mesDA neuroblasts, but not in the differentiated mesDA neurons. From other studies, we know that Ngn2 is involved in the generation of mesDA neurons and that the development of mesDA neurons is severely compromised in Ngn2-null mutant mice. We show here that cells isolated by FACS from the developing VM of Ngn2-GFP knock-in mice are capable of generating mesDA neurons, both in vitro and after transplantation to the striatum of neonatal rats. All mesDA neuron precursors, but not the serotonergic or GABAergie neuron precursors, are contained in the Ngn2-GFP-expressing population. Moreover, all glial cells were generated from cells contained in the GFP-negative cell fraction. The results show that surviving mesDA neurons in VM grafts are derived from early postmitotic, probably Nurr1-expressing precursors before they have acquired their fully differentiated neuronal phenotype. The Ngn2-GFP reporter construct used here thus provides a tool for the identification of inesDA neuron precursors in the VM and selective isolation of transplantable mesDA neuron precursors for transplantation. (c) 2005 Elsevier Inc. All rights reserved. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
FACS, cell sorting, Parkinson's disease, transplantation
in
Experimental Neurology
volume
198
issue
1
pages
183 - 198
publisher
Academic Press
external identifiers
  • pmid:16438966
  • wos:000235747000019
  • scopus:32644440952
ISSN
0014-4886
DOI
10.1016/j.expneurol.2005.11.025
language
English
LU publication?
yes
id
bae64e4f-14b2-4d4b-acd8-eb50a13fc395 (old id 150119)
alternative location
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=16438966&dopt=Abstract
date added to LUP
2007-07-19 15:51:59
date last changed
2019-04-13 02:17:00
@article{bae64e4f-14b2-4d4b-acd8-eb50a13fc395,
  abstract     = {In neural transplantation studies, there is an interest in identifying and isolating mesencephalic dopamine (mesDA) neuron precursors that have the capacity to differentiate into fully mature mesDA neurons after transplantation. We report here that in the developing ventral mesencephalon (VM) the proneural gene Neurogenin2 (Ngn2) is expressed exclusively in the part of the ventricular zone that gives rise to the migrating mesDA neuroblasts, but not in the differentiated mesDA neurons. From other studies, we know that Ngn2 is involved in the generation of mesDA neurons and that the development of mesDA neurons is severely compromised in Ngn2-null mutant mice. We show here that cells isolated by FACS from the developing VM of Ngn2-GFP knock-in mice are capable of generating mesDA neurons, both in vitro and after transplantation to the striatum of neonatal rats. All mesDA neuron precursors, but not the serotonergic or GABAergie neuron precursors, are contained in the Ngn2-GFP-expressing population. Moreover, all glial cells were generated from cells contained in the GFP-negative cell fraction. The results show that surviving mesDA neurons in VM grafts are derived from early postmitotic, probably Nurr1-expressing precursors before they have acquired their fully differentiated neuronal phenotype. The Ngn2-GFP reporter construct used here thus provides a tool for the identification of inesDA neuron precursors in the VM and selective isolation of transplantable mesDA neuron precursors for transplantation. (c) 2005 Elsevier Inc. All rights reserved.},
  author       = {Thompson, Lachlan and Andersson, Elin and Hebsgaard, Josephine and Barraud, Perrine and Guillemot, Francois and Parmar, Malin and Björklund, Anders},
  issn         = {0014-4886},
  keyword      = {FACS,cell sorting,Parkinson's disease,transplantation},
  language     = {eng},
  number       = {1},
  pages        = {183--198},
  publisher    = {Academic Press},
  series       = {Experimental Neurology},
  title        = {Neurogenin2 identifies a transplantable dopamine neuron precursor in the developing ventral mesencephalon.},
  url          = {http://dx.doi.org/10.1016/j.expneurol.2005.11.025},
  volume       = {198},
  year         = {2006},
}