Gata2 specifies serotonergic neurons downstream of sonic hedgehog
Gata2 specifies serotonergic neurons downstream of sonic hedgehog
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DOI：
10.1242/dev.01024
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发表时间：
2004-03-01
期刊：
影响因子：
4.6
通讯作者：
Rosenthal, A
中科院分区：
文献类型：
--
作者：
Craven, SE;Lim, KC;Rosenthal, A
不同种类的多巴胺能（5-HT）神经元沿脊椎动物后脑的腹侧中线沿着发育。在这里，我们确定了一个音刺猬（Shh）调节级联的转录因子，其作用是产生一个特定的子集的5-HT神经元。这种转录级联反应足以诱导菱形节1（r1）内的吻侧5-HT神经元，其投射到前脑，但不足以诱导尾侧5-HT神经元，其主要终止于脊髓。在吻侧后脑内，Shh激活的同源结构域蛋白Nkx2.2和Nkx6.1合作诱导密切相关的锌指转录因子Gata 2和Gata 3。Gata 2反过来又是激活转录因子Lmx 1b和Pet 1并诱导r1内5-HT神经元所必需且足够的。与Gata 2相反，Gata 3不需要用于喙部5-HT神经元的规范，并且似乎无法替代Gata 2的丢失。我们的研究结果表明，密切相关的5-HT亚类的身份发生通过不同的反应相邻rostrocaudal祖域广泛的腹诱导剂。
Distinct classes of serotonergic (5-HT) neurons develop along the ventral midline of the vertebrate hindbrain. Here, we identify a Sonic hedgehog (Shh)-regulated cascade of transcription factors that acts to generate a specific subset of 5-HT neurons. This transcriptional cascade is sufficient for the induction of rostral 5-HT neurons within rhombomere 1 (r1), which project to the forebrain, but not for the induction of caudal 5-HT neurons, which largely terminate in the spinal cord. Within the rostral hindbrain, the Shh-activated homeodomain proteins Nkx2.2 and Nkx6.1 cooperate to induce the closely related zinc-finger transcription factors Gata2 and Gata3. Gata2 in turn is necessary and sufficient to activate the transcription factors Lmx1b and Pet1, and to induce 5-HT neurons within r1. In contrast to Gata2, Gata3 is not required for the specification of rostral 5-HT neurons and appears unable to substitute for the loss of Gata2. Our findings reveal that the identity of closely related 5-HT subclasses occurs through distinct responses of adjacent rostrocaudal progenitor domains to broad ventral inducers.