| First Author | Lu C | Year | 2023 |
| Journal | iScience | Volume | 26 |
| Issue | 5 | Pages | 106670 |
| PubMed ID | 37168577 | Mgi Jnum | J:335566 |
| Mgi Id | MGI:7481824 | Doi | 10.1016/j.isci.2023.106670 |
| Citation | Lu C, et al. (2023) Casein kinase 1alpha is required to maintain murine hypothalamic pro-opiomelanocortin expression. iScience 26(5):106670 |
| abstractText | Hypothalamic pro-opiomelanocortin (POMC) neuron development is considered to play an essential role in the development of obesity. However, the underlying mechanisms remain unclear. Casein kinase 1alpha (CK1alpha) was expressed in the embryonic mouse hypothalamus at high levels and colocalized with POMC neurons. CK1alpha deletion in POMC neurons caused weight gain, metabolic defects, and increased food intake. The number of POMC-expressing cells was considerably decreased in Csnk1a1(fl/fl;)POMC(cre) (PKO) mice from embryonic day 15.5 to postnatal day 60, while apoptosis of POMC neurons was not affected. Furthermore, unchanged POMC progenitor cells and a decreased POMC phenotype established CK1alpha function in hypothalamic POMC neuron development. CK1alpha deletion led to elevated Notch intracellular domain (NICD) protein expression, and NICD inhibition rescued the PKO mouse phenotype. In summary, CK1alpha is involved in hypothalamic POMC expression via NICD-POMC signaling, deepening our understanding of POMC neuron development and control of systemic metabolic functions. |
