The role of Tal2 and Tal1 in the differentiation of midbrain GABAergic neuron precursors.
The role of Tal2 and Tal1 in the differentiation of midbrain GABAergic neuron precursors.
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DOI：
10.1242/bio.20135041
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发表时间：
2013
期刊：
影响因子：
2.4
通讯作者：
Partanen J
中科院分区：
文献类型：
--
作者：
Achim K;Peltopuro P;Lahti L;Tsai HH;Zachariah A;Astrand M;Salminen M;Rowitch D;Partanen J
中脑和后脑来源的GABA能中间神经元对于调节睡眠、呼吸、感觉运动和动机过程至关重要，并且它们与人类神经系统疾病有关。然而，在中脑-后脑区域产生GABA能神经元多样性的确切机制知之甚少。在这里，我们显示了独特的和重叠的要求相关的bHLH蛋白质Tal 1和Tal 2在GABA能神经发生在中脑。我们发现，Tal 2和Tal 1是专门和顺序激活中脑GABA能神经发生。与Gata 2（中脑GABA能神经元身份的有丝分裂后选择者）类似，Tal 2表达在GABA能神经元分化期间非常早地被激活。虽然Tal 2和Gata 2基因的表达是相互独立的，但Tal 2可能是Gata 2的伙伴，对正常中脑GABA能神经发生是重要的。在缺乏Tal 2的情况下，大多数中脑GABA能神经元转变为类神经元表型。相反，Tal 1的表达在更成熟的中脑GABA能神经元前体中以Gata 2和Tal 2依赖的方式被激活，但Tal 1单独不是从中脑神经上皮分化GABA能神经元所需的。然而，Tal 2和Tal 1在发育中的中脑中的失活表明这两个因子合作指导特定腹外侧中脑域中的GABA能神经元分化。Tal 1/Tal 2和Gata 2突变体之间所观察到的相似性和差异表明，这些因素在确定中脑GABA能神经元身份方面既有合作作用，又有独特作用。
Midbrain- and hindbrain-derived GABAergic interneurons are critical for regulation of sleep, respiratory, sensory-motor and motivational processes, and they are implicated in human neurological disorders. However, the precise mechanisms that underlie generation of GABAergic neuron diversity in the midbrain–hindbrain region are poorly understood. Here, we show unique and overlapping requirements for the related bHLH proteins Tal1 and Tal2 in GABAergic neurogenesis in the midbrain. We show that Tal2 and Tal1 are specifically and sequentially activated during midbrain GABAergic neurogenesis. Similar to Gata2, a post-mitotic selector of the midbrain GABAergic neuron identity, Tal2 expression is activated very early during GABAergic neuron differentiation. Although the expression of Tal2 and Gata2 genes are independent of each other, Tal2 is important for normal midbrain GABAergic neurogenesis, possibly as a partner of Gata2. In the absence of Tal2, the majority of midbrain GABAergic neurons switch to a glutamatergic-like phenotype. In contrast, Tal1 expression is activated in a Gata2 and Tal2 dependent fashion in the more mature midbrain GABAergic neuron precursors, but Tal1 alone is not required for GABAergic neuron differentiation from the midbrain neuroepithelium. However, inactivation of both Tal2 and Tal1 in the developing midbrain suggests that the two factors co-operate to guide GABAergic neuron differentiation in a specific ventro-lateral midbrain domain. The observed similarities and differences between Tal1/Tal2 and Gata2 mutants suggest both co-operative and unique roles for these factors in determination of midbrain GABAergic neuron identities.
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影响因子：
64.8
作者：
Muroyama, Y;Fujiwara, Y;Rowitch, DH
通讯作者：
Rowitch, DH
DOI：
10.1016/s0169-328x(98)00323-4
发表时间：
1999-02-05
期刊：
MOLECULAR BRAIN RESEARCH
影响因子：
--
作者：
Mori, S;Sugawara, S;Yokota, Y
通讯作者：
Yokota, Y
神经元型特异性信号，用于腹侧对段区域的奖励和惩罚。
影响因子：
64.8
作者：
Cohen, Jeremiah Y.;Haesler, Sebastian;Vong, Linh;Lowell, Bradford B.;Uchida, Naoshige
通讯作者：
Uchida, Naoshige
影响因子：
8
作者：
Cantor, AB;Orkin, SH
通讯作者：
Orkin, SH
影响因子：
4.6
作者：
Craven, SE;Lim, KC;Rosenthal, A
通讯作者：
Rosenthal, A