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Gamma-protocadherins regulate the functional integrity of hypothalamic feeding circuitry in mice
- Source :
-
Developmental Biology . Mar2010, Vol. 339 Issue 1, p38-50. 13p. - Publication Year :
- 2010
-
Abstract
- 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. [Copyright &y& Elsevier]
Details
- Language :
- English
- ISSN :
- 00121606
- Volume :
- 339
- Issue :
- 1
- Database :
- Academic Search Index
- Journal :
- Developmental Biology
- Publication Type :
- Academic Journal
- Accession number :
- 48120196
- Full Text :
- https://doi.org/10.1016/j.ydbio.2009.12.010