S34-2 Basic Helix-Loop-Helix Transcription Factors in Development of Arcuate Neurons

Program: Symposia
Session: S34-Genetic Control of Arcuate Hypothalamic Development, Differentiation and Renewal
Sunday, June 16, 2013: 4:00 PM-5:30 PM
Presentation Start Time: 4:30 PM
Room 206 (Moscone Center)
Siew Lan Ang*
National Institute of Medical Research, London, United Kingdom
Talk Description:

The basic helix loop helix transcription factor Neurogenin 3 (Ngn3) has critical roles in all the major organs in regulating energy balance, such as pancreas, gut and brain. Using Nkx2.1Cre/+;Ngn3flox/flox mice, we demonstrate that early embryonic hypothalamic inactivation of Ngn3 in mice results in rapid post-weaning obesity that is associated with hyperphagia and reduced energy expenditure. This obesity is caused by loss of expression of Pomc in Pomc/Cart neurons in the arcuate nucleus, indicating an incomplete specification of anorexigenic first order neurons. Furthermore, following the onset of obesity both the arcuate and ventromedial hypothalamic nuclei become insensitive to peripheral leptin treatment. This conditional mouse mutant therefore represents a novel model system for obesity associated with over feeding and under activity, and sheds new light on the role of Ngn3 in regulating the specification of hypothalamic neurons controlling energy balance.