Display Settings:


Send to:

Choose Destination
See comment in PubMed Commons below
Dev Biol. 2010 Mar 1;339(1):38-50. doi: 10.1016/j.ydbio.2009.12.010. Epub 2009 Dec 16.

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

Author information

  • 1Department of Biochemistry, Molecular Biology, and Cell Biology, Northwestern University, 2205 Tech Drive, Hogan 2-100, Evanston, IL 60208-3500, USA.


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.

Copyright 2009 Elsevier Inc. All rights reserved.

[PubMed - indexed for MEDLINE]
Free PMC Article

Images from this publication.See all images (7)Free text

Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
Figure 7
PubMed Commons home

PubMed Commons

How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Elsevier Science Icon for PubMed Central
    Loading ...
    Write to the Help Desk