The scheduling of adolescence with Netrin-1 and UNC5C

Author:

Hoops DanielORCID,Kyne Robert F.,Salameh Samer,MacGowan Del,Avramescu Radu G.,Ewing Elise,He Alina T.,Orsini Taylor,Durand Anais,Popescu ChristinaORCID,Zhao Janet M.,Schatz Kelcie C.,Li LiPing,Carroll Quinn E.,Liu Guofa,Paul Matthew J.,Flores Cecilia

Abstract

AbstractDopamine axons are the only axons known to grow during adolescence. Here, using rodent models, we examined how two proteins, Netrin-1 and its receptor, UNC5C, guide dopamine axons towards the prefrontal cortex and shape behaviour. We demonstrate in mice (Mus musculus) that dopamine axons reach the cortex through a transient gradient of Netrin-1 expressing cells – disrupting this gradient reroutes axons away from their target. Using a seasonal model (Siberian hamsters;Phodopus sungorus) we find that mesocortical dopamine development can be regulated by a natural environmental cue (daylength) in a sexually dimorphic manner – delayed in males, but advanced in females. The timings of dopamine axon growth and UNC5C expression are always phase-locked. Adolescence is an ill-defined, transitional period; we pinpoint neurodevelopmental markers underlying this period.

Publisher

Cold Spring Harbor Laboratory

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