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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.

Novel hypophysiotropic AgRP2 neurons and pineal cells revealed by BAC transgenesis in zebrafish