| First Author | Su H | Year | 2010 |
| Journal | Dev Biol | Volume | 339 |
| Issue | 1 | Pages | 38-50 |
| PubMed ID | 20025866 | Mgi Jnum | J:157958 |
| Mgi Id | MGI:4437396 | Doi | 10.1016/j.ydbio.2009.12.010 |
| Citation | Su H, et al. (2010) Gamma-protocadherins regulate the functional integrity of hypothalamic feeding circuitry in mice. Dev Biol 339(1):38-50 |
| abstractText | 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. |
