The Circadian Clock system
All organisms demonstrate a wide variety of behavioral and physiological daily rhythms that are driven by an evolutionary conserved endogenous circadian clock mechanism. Maintenance of circadian rhythms is crucial for the physical and mental wellbeing, and disruption of the rhythms increases susceptibility to diseases and psychiatric disorders. Utilizing the zebrafish model and cutting edge technologies, current research in our laboratory focuses on several aspects of the circadian clock: The function, development, synchronization, localization, and importance of the circadian clock system in the life of the organism.
Hypothalamic Control of food consumption
Appetite and satiety are regulated by the hypothalamus. A key appetite-inducing peptide in the mammalian hypothalamus is agouti-related protein (AgRP). In fish there are two agrp genes: agrp1 and agrp2. To study the biological significance of this duality we generated transgenic lines in which AgRP1 and AgRP2 neurons can be visualized and manipulated. By characterizing these transgenic lines, we localized AgRP1 neurons and their projections in the hypothalamus. We found that the agrp2 gene is expressed in the pineal gland in a previously uncharacterized subgroup of cells. Additionally, we found that agrp2 is expressed in a small group of neurons in the preoptic area that project directly towards the pituitary gland and form an interface with the pituitary vasculature, suggesting an endocrine role for the preoptic AgRP2 neurons. The functional significance of these findings is still unknown. By combining genetic and neuronal manipulations together with behavioral assays we are currently analyzing the functions of these recently characterized AgRP1 and AgRP2 neurons.
Dorsal view of 6-day post fertilization AgRP1 transgenic fish. AgRP1 neurons are localized to the ventral hypothalamus and project to several brain regions.
Hypothalamic Control of Reproduction and its Development
Gonadotropin-releasing hormone (GnRH) neurons are key regulators of reproduction in all vertebrates. These neurons undergo extensive migration during development, from the olfactory placode to the hypothalamus where they stimulate gonadotropin secretion thereby controlling gametogenesis. Correct course of migration, positioning and regulation of these neurons are crucial for reproductive fitness. We study the mechanisms of this neuronal migration, the role of gene associated with hypogonadism in humans, and the regulation of GnRH neurons.