Article

Distinct roles for specific leptin receptor signals in the development of hypothalamic feeding circuits.

The Saban Research Institute, Developmental Neuroscience Program, Children's Hospital Los Angeles, University of Southern California, Los Angeles, California 90027, USA.
Journal of Neuroscience (impact factor: 7.11). 01/2012; 32(4):1244-52. DOI:10.1523/JNEUROSCI.2277-11.2012 pp.1244-52
Source: PubMed

ABSTRACT Circulating hormones influence multiple aspects of hypothalamic development and play a role in directing formation of neural circuits. Leptin is secreted by adipocytes and functions as a key developmental signal that promotes axon outgrowth from the arcuate nucleus (ARH) during a discrete developmental critical period. To determine the cellular mechanisms by which leptin impacts development of hypothalamic circuits, we examined roles for leptin receptor (LepRb) signals in neonatal mice. LepRb, ERK, and STAT3 signaling were required for leptin-stimulated neurite outgrowth from ARH explants in vitro. Neonatal mice with disrupted LepRb→ERK signaling displayed impaired ARH projections but were able to compensate by adulthood. LepRb→STAT3 signaling also plays a role in early circuit formation and controls the ultimate architecture of POMC, but not AgRP, projections. Thus, the developmental actions of leptin on feeding circuits are dependent on LepRb, and distinct signaling pathways are responsible for directing formation of NPY and POMC projections.

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Keywords

adulthood
 
arcuate nucleus
 
ARH explants
 
ARH projections
 
cellular mechanisms
 
circuit formation
 
Circulating hormones influence multiple aspects
 
developmental actions
 
discrete developmental critical period
 
distinct signaling pathways
 
hypothalamic circuits
 
hypothalamic development
 
key developmental signal
 
LepRb→ERK signaling
 
LepRb→STAT3 signaling
 
leptin-stimulated neurite outgrowth
 
neonatal mice
 
neural circuits
 
STAT3 signaling
 
ultimate architecture
 

Sebastien G Bouret