Mar 28, 2020

Comparative Transcriptomic Analyses of Developing Melanocortin Neurons Reveal New Regulators for the Anorexigenic Neuron Identity

The Journal of Neuroscience : the Official Journal of the Society for Neuroscience
Xiameng ChenChen Liu

Abstract

Despite their opposing actions on food intake, POMC and NPY/AgRP neurons in the arcuate nucleus of the hypothalamus (ARH) are derived from the same progenitors that give rise to ARH neurons. However, the mechanism whereby common neuronal precursors subsequently adopt either the anorexigenic (POMC) or the orexigenic (NPY/AgRP) identity remains elusive. We hypothesize that POMC and NPY/AgRP cell fates are specified and maintained by distinct intrinsic factors. In search of them, we profiled the transcriptomes of developing POMC and NPY/AgRP neurons in mice. Moreover, cell-type-specific transcriptomic analyses revealed transcription regulators that are selectively enriched in either population, but whose developmental functions are unknown in these neurons. Among them, we found the expression of the PR domain-containing factor 12 (Prdm12) was enriched in POMC neurons but absent in NPY/AgRP neurons. To study the role of Prdm12 in vivo, we developed and characterized a floxed Prdm12 allele. Selective ablation of Prdm12 in embryonic POMC neurons led to significantly reduced Pomc expression as well as early-onset obesity in mice of either sex that recapitulates symptoms of human POMC deficiency. Interestingly, however, specific deleti...Continue Reading

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Mentioned in this Paper

Gene Deletion
Stem Cells
POMC gene
Obesity
Melanocortins
Finding
CNS - Brain - Hypothalamus (Mmhcc)
POMC
Protein Expression
Structure of Nucleus Infundibularis Hypothalami

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