POMC

Cilia effects upon perturbation of POMC

Ciliogenesis screen results (3 screens)

• Wheway et al. 2015 (siRNA) [siRNA]: No effect PMID:26167766
• Breslow et al. 2018 (CRISPR) [CRISPR]: No Significant Effect PMID:29459680
• Roosing et al. 2015 (siRNA) [siRNA]: No effect PMID:26595381

Phenotypes

Mouse phenotype:

preweaning lethality; incomplete penetrance; impaired glucose tolerance; abnormal spleen morphology; enlarged spleen

Human ciliopathy phenotype:

obesity due to pro-opiomelanocortin deficiency; obesity; Obesity

Subcellular localization

cilia associated gene

Functional category

• Motile cilium & axoneme; Ciliary assembly/disassembly

Function

Inhibition of ciliogenesis in POMC-expressing developing hypothalamic neurons, by depleting ciliogenic genes IFT88 and KIF3A, leads to adulthood obesity in mice. In contrast, adult-onset ciliary dysgenesis in POMC neurons causes no significant change in adiposity. In developing POMC neurons, abnormal cilia formation disrupts axonal projections through impaired lysosomal protein degradation. Notably, maternal nutrition and postnatal leptin surge have a profound impact on ciliogenesis in the hypothalamus of neonatal mice; through these effects they critically modulate the organization of hypothalamic feeding circuits(PMID: 33188191).