Shh maintains NkK2.1 in the MGE by a Gli3-independent mechanism
Shh maintains NkK2.1 in the MGE by a Gli3-independent mechanism
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DOI：
10.1093/cercor/bhk018
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发表时间：
2006-07-01
期刊：
影响因子：
3.7
通讯作者：
Anderson, Stewart A.
中科院分区：
文献类型：
--
作者：
Gulacsi, Alexandra;Anderson, Stewart A.
γ-氨基丁酸能（GABA能）中间神经元在皮质发育和功能中起关键作用。这些角色由不同的中间神经元亚群执行，特定亚群的功能障碍可能导致各种神经精神疾病。在啮齿类动物中，大多数皮质中间神经元起源于苍白球端脑，其也产生纹状体和其他腹侧结构的GABA能神经元。在本文中，我们研究的证据不同的起源interneuron亚群，然后讨论的作用，同源框基因甲状腺转录因子1（Ttf-1或Nkx2.1）的规格interneurons从内侧神经节隆起（MGE）。Nkx2.1在苍白球端脑中通过音刺猬（Shh）的作用诱导，该音刺猬（Shh）拮抗背侧Gli 3阻遏物（Gli 3R）蛋白的形成。最近的证据表明，Shh也需要维持Nkx2.1的表达，从而MGE interneuron规范，在胚胎神经发生。在这里，我们提供的证据表明，在端脑图案的Nkx2.1的初始诱导相反，Nkx2.1的维护功能的Shh不需要阻止Gli 3R的形成。可塑性Nkx2.1表达的年龄范围内的interneuron的发生表明，调节该基因的因素可以是关键的决定因素的平衡，在出生后的大脑皮层的兴奋和抑制。
gamma-Aminobutyric acidergic (GABAergic) interneurons perform crucial roles in cortical development and function. These roles are executed by diverse subgroups of interneurons, and dysfunction of particular subgroups may contribute to a variety of neuropsychiatric diseases. In rodents, most cortical interneurons originate in the pallidal telencephalon that also gives rise to the GABAergic neurons of the striatum and other ventral structures. In this paper, we examine the evidence for distinct origins of interneuron subgroups and then discuss the role of the homeobox gene thyroid transcription factor1 (Ttf-1 or Nkx2.1) in the specification of interneurons from the medial ganglionic eminence (MGE). Nkx2.1 is induced in the pallidal telencephalon by the action of sonic hedgehog (Shh) that antagonizes formation of the dorsalizing Gli3 repressor (Gli3R) protein. Recent evidence suggests that Shh is also required to maintain Nkx2.1 expression, and thus MGE interneuron specification, during embryonic neurogenesis. Here we provide evidence that, in contrast to the initial induction of Nkx2.1 during telencephalic patterning, the Nkx2.1 maintenance function of Shh does not require blocking the formation of the Gli3R. The plastic nature of Nkx2.1 expression during the age range of interneuron genesis suggests that factors regulating this gene can be critical determinants of the balance of excitation and inhibition in the postnatal cerebral cortex.