產(chǎn)生作為神經(jīng)傳輸物質(zhì)多巴胺的神經(jīng)元控制一系列腦功能,，包括運動控制,、認知、動機和快感,。前體細胞在這些功能所涉及的數(shù)量巨大的發(fā)育線路中是怎樣選擇其中一個線路——即選擇多巴胺能這一命運的一直不清楚。
現(xiàn)在,，Nuria Flames 和Oliver Hobert報告說,，調(diào)控蛋白AST-1是線蟲C. elegans體內(nèi)驅(qū)動和維持多巴胺能神經(jīng)元的末端分化的必要和充分條件。由于該蛋白及其末端分化功能在小鼠身上被驚人地保留了下來,，所以這些結果對于多巴胺相關疾病如帕金森氏癥的干細胞替換療法有直接意義,。（生物谷Bioon.com）
生物谷推薦原始出處：
Nature 458, 885-889 (16 April 2009) | doi:10.1038/nature07929
Gene regulatory logic of dopamine neuron differentiation
Nuria Flames1 & Oliver Hobert1
Howard Hughes Medical Institute, Department of Biochemistry and Molecular Biophysics, Columbia University Medical Center, New York, New York 10032, USA
Dopamine signalling regulates a variety of complex behaviours, and defects in dopamine neuron function or survival result in severe human pathologies, such as Parkinson's disease1. The common denominator of all dopamine neurons is the expression of dopamine pathway genes, which code for a set of phylogenetically conserved proteins involved in dopamine synthesis and transport. Gene regulatory mechanisms that result in the direct activation of dopamine pathway genes and thereby ultimately determine the identity of dopamine neurons are poorly understood in all systems studied so far2. Here we show that a simple cis-regulatory element, the dopamine (DA) motif, controls the expression of all dopamine pathway genes in all dopaminergic cell types in Caenorhabditis elegans. The DA motif is activated by the ETS transcription factor AST-1. Loss of ast-1 results in the failure of all distinct dopaminergic neuronal subtypes to terminally differentiate. Ectopic expression of ast-1 is sufficient to activate the dopamine pathway in some cellular contexts. Vertebrate dopamine pathway genes also contain phylogenetically conserved DA motifs that can be activated by the mouse ETS transcription factor Etv1 (also known as ER81), and a specific class of dopamine neurons fails to differentiate in mice lacking Etv1. Moreover, ectopic Etv1 expression induces dopaminergic fate marker expression in neuronal primary cultures. Mouse Etv1 can also functionally substitute for ast-1 in C. elegans. Our studies reveal a simple and apparently conserved regulatory logic of dopamine neuron terminal differentiation and may provide new entry points into the diagnosis or therapy of conditions in which dopamine neurons are defective.
