Novel hypophysiotropic AgRP2 neurons and pineal cells revealed by BAC transgenesis in zebrafish.
Novel hypophysiotropic AgRP2 neurons and pineal cells revealed by BAC transgenesis in zebrafish.
复制标题
DOI：
10.1038/srep44777
复制
发表时间：
2017-03-20
影响因子：
4.6
通讯作者：
Gothilf Y
中科院分区：
文献类型：
--
作者：
Shainer I;Buchshtab A;Hawkins TA;Wilson SW;Cone RD;Gothilf Y
神经肽刺鼠相关蛋白(AgRP)表达于哺乳动物下丘脑的弓状核，在调节食物消耗和能量平衡方面起着关键作用。鱼类在大脑中表达两个AgRP基因：agrp1和agrp2。agrp1被认为与哺乳动物的agrp在功能上同源。Agrp2的作用及其与agrp1的关系尚不完全清楚。利用BAC转基因，我们获得了转基因斑马鱼，其中agrp1和agrp2的表达细胞可以被可视化和操纵。通过对这些转基因株系的鉴定，我们发现agrp1表达的神经元位于下丘脑室旁腹侧(相当于哺乳动物的弓状核)，投射到整个下丘脑和视前区。Agrp2基因在松果体中的一个以前没有特征的细胞亚群中表达。此外，AgRP2在视前区的一小群神经元中表达，这些神经元直接投射到垂体并与垂体血管系统形成界面，表明视前AgRP2神经元是促垂性的。我们发现在下丘脑的AgRP1和AgRP2神经元之间可以存在直接的突触联系，这表明AgRP1和AgRP2神经元之间以及它们所调控的过程之间可能存在着沟通和协调。
The neuropeptide agouti-related protein (AgRP) is expressed in the arcuate nucleus of the mammalian hypothalamus and plays a key role in regulating food consumption and energy homeostasis. Fish express two agrp genes in the brain: agrp1, considered functionally homologous with the mammalian AgRP, and agrp2. The role of agrp2 and its relationship to agrp1 are not fully understood. Utilizing BAC transgenesis, we generated transgenic zebrafish in which agrp1- and agrp2-expressing cells can be visualized and manipulated. By characterizing these transgenic lines, we showed that agrp1-expressing neurons are located in the ventral periventricular hypothalamus (the equivalent of the mammalian arcuate nucleus), projecting throughout the hypothalamus and towards the preoptic area. The agrp2 gene was expressed in the pineal gland in a previously uncharacterized subgroup of cells. Additionally, agrp2 was expressed in a small group of neurons in the preoptic area that project directly towards the pituitary and form an interface with the pituitary vasculature, suggesting that preoptic AgRP2 neurons are hypophysiotropic. We showed that direct synaptic connection can exist between AgRP1 and AgRP2 neurons in the hypothalamus, suggesting communication and coordination between AgRP1 and AgRP2 neurons and, therefore, probably also between the processes they regulate.