Novel hypophysiotropic AgRP2 neurons and pineal cells revealed by BAC transgenesis in zebrafish.
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.
Department of Neurobiology, George S. Wise Faculty of Life Sciences, Tel-Aviv University, Tel-Aviv, Israel.
Inbal
I
Shainer
Department of Neurobiology, George S. Wise Faculty of Life Sciences, Tel-Aviv University, Tel-Aviv, Israel.
Adi
A
Buchshtab
The Department of Cell and Developmental Biology, Faculty of Life Sciences, University College London, London, UK.
Thomas A
TA
Hawkins
The Department of Cell and Developmental Biology, Faculty of Life Sciences, University College London, London, UK.
Stephen W
SW
Wilson
Life Sciences Institute, University of Michigan, Ann Arbor, MI, USA.
Roger D
RD
Cone
Department of Neurobiology, George S. Wise Faculty of Life Sciences, Tel-Aviv University, Tel-Aviv, Israel.|Sagol School of Neuroscience, Tel-Aviv University, Tel-Aviv, Israel.
Yoav
Y
Gothilf
D054369:Agouti-Related Protein / Q000378:metabolism*; D000818:Animals; D030801:Animals, Genetically Modified; D002450:Cell Communication; D022202:Chromosomes, Artificial, Bacterial / Q000235:genetics*; D018014:Gene Transfer Techniques; D009474:Neurons / Q000378:metabolism*; D010870:Pineal Gland / Q000166:cytology*; D010902:Pituitary Gland / Q000378:metabolism*; D011301:Preoptic Area / Q000378:metabolism; D015027:Zebrafish / Q000235:genetics*
D054369:Agouti-Related Protein