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Loss of the centrosomal protein Cenpj leads to dysfunction of the hypothalamus and obesity in mice

Science China(Life Sciences) 2021年第3期64卷 419-433页

作者： Wenyu Ding Changjiang Zhang Baisong Wang Xin Zhou Le Sun Suijuan Zhong Jing Liu Junjing Zhang Xiaoqun Wang Qian Wu State Key Laboratory of Cognitive Neuroscience and Learning Beijing Normal UniversityBeijing 100875China IDG/McGovern Institute for Brain Research Beijing Normal UniversityBeijing 100875China State Key Laboratory of Brain and Cognitive Science CAS Center for Excellence in Brain Science and Intelligence TechnologyInstitute of Brain-Intelligence Technology(Shanghai)Institute of BiophysicsChinese Academy of SciencesBeijing 100101China University of Chinese Academy of Sciences Beijing 100049China Institute for Stem Cell and Regeneration Chinese Academy of SciencesBeijing 100101China Advanced Innovation Center for Human Brain Protection Beijing Institute for Brain DisordersCapital Medical UniversityBeijing 100069China

Cenpj is a centrosomal protein located at the centrosomes and the base of cilia,it plays essential roles in regulating neurogenesis and cerebral cortex development.Although centrosomal and cilium dysfunction are one of the causes of obesity,insulin resistance,and type 2 diabetes,the role that Cenpj plays in the regulation of body weight remains unclear.Here,we deleted Cenpj by crossing Cenpjflox/flox mice with Nkx2.1-Cre mice.Loss of the centrosomal protein Cenpj in Nkx2.1-expressing cells causes morbid obesity in mice at approximately 4 months of age with expended brain ventricles but no change of brain size.We found that hypothalamic cells exhibited reduced proliferation and increased apoptosis upon Cenpj depletion at the embryonic stages,resulting in a dramatic decrease in the number of Proopiomelanocortin(POMC)neurons and electrophysiological dysfunction of NPY neurons in the arcuate nucleus(ARC)in adults.Furthermore,depletion of Cenpj also reduced the neuronal projection from the ARC to the paraventricular nucleus(PVN),with decreased melanocortin-4 receptors(MC4R)expression in PVN neurons.The study defines the roles that Cenpj plays in regulating hypothalamus development and body weight,providing a foundation for further understanding of the pathological mechanisms of related diseases.

关键词： arcuate nucleus centrosomal protein Cenpj Nkx2.1 hypothalamus paraventricular nucleus

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