Ascl1/Mash1 is required for the development of central serotonergic neurons

Ascl1/Mash1 is required for the development of central serotonergic neurons
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DOI:
10.1038/nn1247
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发表时间:
2004-06-01
影响因子:
25
通讯作者:
Brunet, JF
Brunet, JF
中科院分区:
医学1区
文献类型:
--
作者:
Pattyn, A;Simplicio, N;Brunet, JF

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脊椎动物中枢5-羟色胺能神经元分化的转录调控最近受到关注,并已被证明涉及同源框基因Nkx 2 -2和Lmx 1b,Ets结构域基因Pet 1(也称为Fev)和锌指基因Gata 3。碱性螺旋-环-螺旋(bHLH)基因Ascl 1(也称为Mash 1)与Nkx 2 -2在后脑的神经上皮结构域中共表达,其产生5-HT神经元。在这里,我们表明,在小鼠中,Ascl 1是必不可少的5-HT神经元的诞生,无论是作为一个proneural基因的有丝分裂后神经元前体的生产和作为一个决定因素的Gata 3,Lmx 1b和Pet 1的平行激活的cadronergic表型。因此,Ascl 1,这是去甲肾上腺素能分化所必需的,也是肾上腺素能表型的决定因素。
The transcriptional control of the differentiation of central serotonergic (5-HT) neurons in vertebrates has recently come under scrutiny and has been shown to involve the homeobox genes Nkx2-2 and Lmx1b, the Ets-domain gene Pet1 (also known as Fev) and the zinc-finger gene Gata3. The basic helix-loop-helix (bHLH) gene Ascl1 (also known as Mash1) is coexpressed with Nkx2-2 in the neuroepithelial domain of the hindbrain, which gives rise to 5-HT neurons. Here we show in the mouse that Ascl1 is essential for the birth of 5-HT neurons, both as a proneural gene for the production of postmitotic neuronal precursors and as a determinant of the serotonergic phenotype for the parallel activation of Gata3, Lmx1b and Pet1. Thus Ascl1, which is essential for noradrenergic differentiation, is also a determinant of the serotonergic phenotype.