Information Services banner Edinburgh Research Archive The University of Edinburgh crest

Edinburgh Research Archive >
Biological Sciences, School of >
Biological Sciences publications >

Please use this identifier to cite or link to this item: http://hdl.handle.net/1842/1358

This item has been viewed 28 times in the last year. View Statistics

Files in This Item:

File Description SizeFormat
Appendix 7 elec.pdf917.88 kBAdobe PDFView/Open
Title: Pitx3 regulates tyrosine hydroxylase expression in the substantia nigra and identifies a subgroup of mesencephalic dopaminergic progenitor neurons during mouse development
Authors: Maxwell, Sarah L
Ho, Hsin-Yi
Kuehner, Eva
Zhao, Suling
Li, Meng
Issue Date: 2005
Citation: Developmental Biology, Volume: 282 Page: 467 – 479
Publisher: Elsevier
Abstract: Recent studies of mouse mutant aphakia have implicated the homeobox gene Pitx3 in the survival of substantia nigra dopaminergic neurons, the degeneration of which causes Parkinson’s disease. To directly investigate a role for Pitx3 in midbrain DA neuron development, we have analyzed a line of Pitx3-null mice that also carry an eGFP reporter under the control of the endogenous Pitx3 promoter. We show that the lack of Pitx3 resulted in a loss of nascent substantia nigra dopaminergic neurons at the beginning of their final differentiation. Pitx3 deficiency also caused a loss of tyrosine hydroxylase (TH) expression specifically in the substantia nigra neurons. Therefore, our study provides the first direct evidence that the aphakia allele of Pitx3 is a hypomorph and that Pitx3 is required for the regulation of TH expression in midbrain dopaminergic neurons as well as the generation and/or maintenance of these cells. Furthermore, using the targeted GFP reporter as a midbrain dopaminergic lineage marker, we have identified previously unrecognised ontogenetically distinct subpopulations of dopaminergic cells within the ventral midbrain based on their temporal and topographical expression of Pitx3 and TH. Such an expression pattern may provide the molecular basis for the specific dependence of substantia nigra DA neurons on Pitx3.
Keywords: Differentiation
Dopaminergic neuron
Embryonic stem cell
GFP
Homeobox
knock-in
Pitx3
Tyrosine hydroxylase
Transcription factor
URI: DOI: 10.1016/j.ydbio.2005.03.028
http://hdl.handle.net/1842/1358
Appears in Collections:Biological Sciences publications

Items in ERA are protected by copyright, with all rights reserved, unless otherwise indicated.

 

Valid XHTML 1.0! Unless explicitly stated otherwise, all material is copyright © The University of Edinburgh 2013, and/or the original authors. Privacy and Cookies Policy