title: Gamma-protocadherins regulate the functional integrity of hypothalamic feeding circuitry in mice.
abstract: The hypothalamic neuronal circuits that modulate energy homeostasis become mature and functional during early postnatal life. However, the molecular mechanism underlying this developmental process remains largely unknown. Here we use a mouse genetic approach to investigate the role of gamma-protocadherins (Pcdh-gammas) in hypothalamic neuronal circuits. First, we show that rat insulin promoter (RIP)-Cre conditional knockout mice lacking Pcdh-gammas in a broad subset of hypothalamic neurons are obese and hyperphagic. Second, specific deletion of Pcdh-gammas in anorexigenic proopiomelanocortin (POMC) expressing neurons also leads to obesity. Using cell lineage tracing, we show that POMC and RIP-Cre expressing neurons do not overlap but interact with each other in the hypothalamus. Moreover, excitatory synaptic inputs are reduced in Pcdh-gamma deficient POMC neurons. Genetic evidence from both knockout models shows that Pcdh-gammas can regulate POMC neuronal function autonomously and non-autonomously through cell-cell interaction. Taken together, our data demonstrate that Pcdh-gammas regulate the formation and functional integrity of hypothalamic feeding circuitry in mice.
authors.affiliation: Department of Biochemistry, Molecular Biology, and Cell Biology, Northwestern University, 2205 Tech Drive, Hogan 2-100, Evanston, IL 60208-3500, USA.
authors.forename: Hong
authors.initials: H
authors.lastname: Su
authors.forename: Biliana
authors.initials: B
authors.lastname: Marcheva
authors.forename: Shuxia
authors.initials: S
authors.lastname: Meng
authors.forename: Fengxia A
authors.initials: FA
authors.lastname: Liang
authors.forename: Akira
authors.initials: A
authors.lastname: Kohsaka
authors.forename: Yumiko
authors.initials: Y
authors.lastname: Kobayashi
authors.forename: Allison W
authors.initials: AW
authors.lastname: Xu
authors.forename: Joseph
authors.initials: J
authors.lastname: Bass
authors.forename: Xiaozhong
authors.initials: X
authors.lastname: Wang
mesh_terms: D000818:Animals; D000070585:Cadherin Related Proteins; D015820:Cadherins / Q000235:genetics / Q000502:physiology*; D019070:Cell Lineage; D004734:Energy Metabolism; D005247:Feeding Behavior / Q000502:physiology*; D007031:Hypothalamus / Q000166:cytology / Q000502:physiology*; D007150:Immunohistochemistry; D007515:Islets of Langerhans / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D016253:Microscopy, Immunoelectron; D009474:Neurons / Q000166:cytology; D016133:Polymerase Chain Reaction
chemical_list: D000070585:Cadherin Related Proteins; D015820:Cadherins; C464785:Gamma-protocadherins