Gamma-protocadherins regulate the functional integrity of hypothalamic feeding circuitry in mice

Hong Su, Biliana Marcheva, Shuxia Meng, Fengxia A. Liang, Akira Kohsaka, Yumiko Kobayashi, Allison W. Xu, Joseph Bass, Xiaozhong Wang*

*Corresponding author for this work

Research output: Contribution to journalArticle

21 Scopus citations

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-γs) in hypothalamic neuronal circuits. First, we show that rat insulin promoter (RIP)-Cre conditional knockout mice lacking Pcdh-γs in a broad subset of hypothalamic neurons are obese and hyperphagic. Second, specific deletion of Pcdh-γs 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-γ deficient POMC neurons. Genetic evidence from both knockout models shows that Pcdh-γs can regulate POMC neuronal function autonomously and non-autonomously through cell-cell interaction. Taken together, our data demonstrate that Pcdh-γs regulate the formation and functional integrity of hypothalamic feeding circuitry in mice.

Original languageEnglish (US)
Pages (from-to)38-50
Number of pages13
JournalDevelopmental Biology
Volume339
Issue number1
DOIs
StatePublished - Mar 2010

Keywords

  • Development
  • Hypothalamus
  • Neuron
  • Protocadherin
  • Synapse

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology
  • Cell Biology

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