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[ST4]: Dopaminergic neuronal cluster size is determined during early forebrain patterning
Author(s) -
RussekBlum N.,
Gutnick A.,
NabelRosen H.,
Houart C.,
Dorsky R.,
Levkowitz G.
Publication year - 2008
Publication title -
international journal of developmental neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.761
H-Index - 88
eISSN - 1873-474X
pISSN - 0736-5748
DOI - 10.1016/j.ijdevneu.2008.09.030
Subject(s) - citation , library science , computer science
sufficient for the development of dopamine neurons, in embryonic midbrain progenitors and embryonic stem cells. Foxa2 continues to be expressed in dopamine neurons in the adult mouse brain. In old, foxa2-heterozygous, mutant mice, we observe the spontaneous appearance of motor deficits; this movement disorder is accompanied by a loss of dopamine neurons. A loss of dopamine neurons is characteristic of Parkinson’s Disease (PD) and additional features of the dopamine neuron loss in mutantmice are reminiscent of PD. This is the firstmousemodel of spontaneous, age-dependent dopamine neuron degeneration. Targeting the survival function of the foxa2 gene may prove important in stem cell-based and pharmacological approaches to dopamine neuron disease. Stem cell biology, embryology, and this animal model of PD suggest that foxa2 is a critical gene during multiple windows of the ‘‘molecular biography’’ of the dopamine neuron. Our results suggest that the stem cell approach can shed valuable insights, not only in the realm of developmental biology, but, also, into the mechanisms of human degenerative disease.