Brn3a and Nurr1 mediate a gene regulatory pathway for habenula development.
Brn3a and Nurr1 mediate a gene regulatory pathway for habenula development.
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DOI：
10.1523/jneurosci.2430-09.2009
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发表时间：
2009-11-11
期刊：
影响因子：
--
通讯作者：
Turner EE
中科院分区：
文献类型：
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作者：
Quina LA;Wang S;Ng L;Turner EE
缰核是一个背侧间脑结构，由内侧和外侧亚核以及主要的输出束，即反曲束组成，它们共同形成边缘前脑和腹侧中脑之间的联系。在这里，我们已经在小鼠中使用微阵列和生物信息学的方法，以表明缰是一个独特的分子领域的中枢神经系统，具有独特的配置文件的神经递质，离子通道和调节因子的表达。内侧缰核和部分外侧缰核的神经元表达转录因子Brn 3a/Pou 4f 1，表达Brn 3a的缰核神经元仅投射到中脑腹侧脚间核。在Brn 3a突变体胚胎的反曲束是正确的，但缰神经元不能支配他们的目标。Brn 3anull胚胎的微阵列分析表明，该因子调节了富含缰核的基因的广泛程序，但不调节一般神经特性。孤儿核受体Nurr 1/Nr 4a 2在发育中的缰核中与Brn 3a共表达，位于Brn 3a的下游，并介导Brn 3a调节转录物的子集的表达。这些发现开始共同定义哺乳动物缰核发育的基因调控途径。
The habenula is a dorsal diencephalic structure consisting of medial and lateral subnuclei and a principal output tract, the fasciculus retroflexus, which together form a link between the limbic forebrain and ventral midbrain. Here we have used microarray and bioinformatic approaches in the mouse to show that the habenula is a distinctive molecular territory of the CNS, with a unique profile of neurotransmitter, ion channel, and regulatory factor expression. Neurons of the medial habenula and part of the lateral habenula express the transcription factor Brn3a/Pou4f1, and Brn3a-expressing habenular neurons project exclusively to the interpeduncular nucleus in the ventral midbrain. In Brn3a mutant embryos the fasciculus retroflexus is directed appropriately, but habenular neurons fail to innervate their targets. Microarray analysis of Brn3anull embryos shows that this factor regulates an extensive program of habenula-enriched genes, but not generic neural properties. The orphan nuclear receptor Nurr1/Nr4a2 is co-expressed with Brn3a in the developing habenula, is downstream of Brn3a, and mediates expression of a subset of Brn3a regulated transcripts. Together these findings begin to define a gene regulatory pathway for habenula development in mammals.