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The current studies assessed potential amylin and amylin-leptin ARC\/VMN interactions on ERK signaling and their roles in postnatal hypothalamic pathway development. In amylin knockout mice, the density of agouti-related protein (AgRP)-immunoreactive (IR) fibers in the hypothalamic paraventricular nucleus (PVN) was increased, while the density of \u03b1-melanocyte\u2013stimulating hormone (\u03b1MSH) fibers was decreased. In mice deficient of the amylin receptor components RAMP1\/3, both AgRP and \u03b1MSH-IR fiber densities were decreased, while only \u03b1MSH-IR fiber density was decreased in rats injected neonatally in the ARC\/VMN with an adeno-associated virus short hairpin RNA against the amylin core receptor. Amylin induced p-ERK in ARC neurons, 60% of which was present in POMC-expressing neurons, with none in NPY neurons. An amylin-leptin interaction was shown by an additive effect on ARC ERK signaling in neonatal rats and a 44% decrease in amylin-induced p-ERK in the ARC of leptin receptor\u2013deficient and of ob\/ob mice. Together, these results suggest that amylin directly acts, through a p-ERK\u2013mediated process, on POMC neurons to enhance ARC-PVN \u03b1MSH pathway development.<\/jats:p>","DOI":"10.2337\/db17-1347","type":"journal-article","created":{"date-parts":[[2018,2,22]],"date-time":"2018-02-22T01:35:18Z","timestamp":1519263318000},"page":"805-817","update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":70,"title":["Amylin Selectively Signals Onto POMC Neurons in the Arcuate Nucleus of the Hypothalamus"],"prefix":"10.2337","volume":"67","author":[{"given":"Thomas A.","family":"Lutz","sequence":"first","affiliation":[{"name":"Institute of Veterinary Physiology, University of Zurich, Zurich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernd","family":"Coester","sequence":"additional","affiliation":[{"name":"Institute of Veterinary Physiology, University of Zurich, Zurich, 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