The Function Of COUP-TFâ…¡ Gene In The Development Of Mouse Paraventricular Nucleus Of Hypothalamus

The cause of obesity is the imbalance between the interaction of the internal energy balance system and the external environment factors. Food intake and energy expenditure are the two most imperative factors involved in energy balance, which are regulated by the central nervous system, especially hypothalamus. We observed that COUP-TFII gene was highly expressed in hypothalamic regions at E10.5, E12.5 and E14.5. However, so far whether and how COUP-TFII gene participates in the development of the hypothalamus are still largely unclear. In this study, by using RXCre mouse model, we obtained the ventral forebrain specific COUP-TFII gene conditional knockout(RXCre/+; COUP-TFIIF/F) mutant mice. COUP-TFII gene knockout mutant mice showed abnormal growth curve and plasma glucose levels. H&E staining and immunohistochemical assays revealed that the development of PVH nucleus is compromised, accompanying with sharply reduced Brn2+ PVH neurons. Double immunofluorescence assays demonstrated that COUP-TFII and Brn2 proteins are only co-expressed in the PVH neural progenitor cells or the early differentiating PVH neurons, but not in the mature PVH neurons. Mechanistic studies revealed that COUP-TFII gene may prevent the apoptosis of Brn2+ PVH neurons by regulating the expression of BDNF gene. Our study reveals the mechanism of COUP-TFII gene in the development of PVH nucleus, which may benefit the understanding of the etiology and the therapy of the abnormal metabolic disorders, such as obesity.