|  Help  |  About  |  Contact Us

Publication : Ciliary gene RPGRIP1L is required for hypothalamic arcuate neuron development.

First Author  Wang L Year  2019
Journal  JCI Insight Volume  4
Issue  3 PubMed ID  30728336
Mgi Jnum  J:309339 Mgi Id  MGI:6754280
Doi  10.1172/jci.insight.123337 Citation  Wang L, et al. (2019) Ciliary gene RPGRIP1L is required for hypothalamic arcuate neuron development. JCI Insight 4(3)
abstractText  Intronic polymorphisms in the alpha-ketoglutarate-dependent dioxygenase gene (FTO) that are highly associated with increased body weight have been implicated in the transcriptional control of a nearby ciliary gene, retinitis pigmentosa GTPase regulator-interacting protein-1 like (RPGRIP1L). Previous studies have shown that congenital Rpgrip1l hypomorphism in murine proopiomelanocortin (Pomc) neurons causes obesity by increasing food intake. Here, we show by congenital and adult-onset Rpgrip1l deletion in Pomc-expressing neurons that the hyperphagia and obesity are likely due to neurodevelopmental effects that are characterized by a reduction in the Pomc/Neuropeptide Y (Npy) neuronal number ratio and marked increases in arcuate hypothalamic-paraventricular hypothalamic (ARH-PVH) axonal projections. Biallelic RPGRIP1L mutations result in fewer cilia-positive human induced pluripotent stem cell-derived (iPSC-derived) neurons and blunted responses to Sonic Hedgehog (SHH). Isogenic human ARH-like embryonic stem cell-derived (ESc-derived) neurons homozygous for the obesity-risk alleles at rs8050136 or rs1421085 have decreased RPGRIP1L expression and have lower numbers of POMC neurons. RPGRIP1L overexpression increases POMC cell number. These findings suggest that apparently functional intronic polymorphisms affect hypothalamic RPGRIP1L expression and impact development of POMC neurons and their derivatives, leading to hyperphagia and increased adiposity.
Quick Links:
 
Quick Links:
 

Expression

Publication --> Expression annotations

 

Other

29 Bio Entities

Trail: Publication

0 Expression