| Hypothalamus regulates the homeostasis of animals and participates in the structural and functional emotion circuits.NROB1 gene expresses specifically in the hypothalamus of both humans and mice. As an unusual orphan nuclear receptor, NROBI has conserved functions in regulating gonadal development and sexual determination in vertebrates that when mutated causes adrenal hypoplasia congenita(AHC) with associated hypogonadotropic hypogonadism(HH), and when duplicated causes dosage sensitive sex reversal(DSS). However, the projection of hypothalamic NROBI neurons and the functions of NROBI gene in regulating physiology and behavior are not well studied. As a vertebrate model systems, the genetic makeup of the zebrafish shares high degree of homology with higher vertebrate including human. The central nervous system of zebrafish also has similarity to that of the mammalian animals and is readily amenable to genetic manipulations. More recently, taking advantage of transgenic and knockout lines, zebrafish has increasingly been used in studies of neuroscience related areas. We screened out nrOb1 knockout line t313 and the transgene line s313 that specifically labeled the nrOb1 neurons in the ventral hypothalamus to study the projection of nrob1neurons and the function of nrObl gene.Results from our preliminary studies shownrOb1neurons send projections to various regions within the brain and express several kinds of neuropeptide, including pdyn, pomca, pomcb, agrp, cart, tacl and sst3. Fluorescence in situ hybridization (FISH) shows well collocalization expression ofnrObl and pdyn gene. The results of nrObl knockdown, overexpress and knockout all prove nrObl can repress pdyn expression in the ventral hypothalamus. This study will help elucidate the connections between hypothalamic nrObl neurons and other brain regions. Results from this proposal will also build the foundation for further investigation of nrOb1 gene functions and underlying mechanism of regulating physiology and behaviors. |
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