title: Distinct roles for specific leptin receptor signals in the development of hypothalamic feeding circuits.
abstract: Circulating hormones influence multiple aspects of hypothalamic development and play a role in directing formation of neural circuits. Leptin is secreted by adipocytes and functions as a key developmental signal that promotes axon outgrowth from the arcuate nucleus (ARH) during a discrete developmental critical period. To determine the cellular mechanisms by which leptin impacts development of hypothalamic circuits, we examined roles for leptin receptor (LepRb) signals in neonatal mice. LepRb, ERK, and STAT3 signaling were required for leptin-stimulated neurite outgrowth from ARH explants in vitro. Neonatal mice with disrupted LepRb→ERK signaling displayed impaired ARH projections but were able to compensate by adulthood. LepRb→STAT3 signaling also plays a role in early circuit formation and controls the ultimate architecture of POMC, but not AgRP, projections. Thus, the developmental actions of leptin on feeding circuits are dependent on LepRb, and distinct signaling pathways are responsible for directing formation of NPY and POMC projections.
authors.affiliation: The Saban Research Institute, Developmental Neuroscience Program, Children's Hospital Los Angeles, University of Southern California, Los Angeles, California 90027, USA. sbouret@chla.usc.edu
authors.forename: Sebastien G
authors.initials: SG
authors.lastname: Bouret
authors.forename: Sarah H
authors.initials: SH
authors.lastname: Bates
authors.forename: Stephen
authors.initials: S
authors.lastname: Chen
authors.forename: Martin G
authors.initials: MG
authors.lastname: Myers
authors.forename: Richard B
authors.initials: RB
authors.lastname: Simerly
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D005247:Feeding Behavior / Q000502:physiology*; D006801:Humans; D007031:Hypothalamus / Q000254:growth & development* / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009415:Nerve Net / Q000254:growth & development* / Q000502:physiology; D009434:Neural Pathways / Q000502:physiology; D009924:Organ Culture Techniques; D054411:Receptors, Leptin / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*
chemical_list: D054411:Receptors, Leptin; C515447:leptin receptor, mouse