<i>Mir505–3p</i> regulates axonal development via inhibiting the autophagy pathway by targeting <i>Atg12</i>

In addition to the canonical role in protein homeostasis, autophagy has recently been found to be involved in axonal dystrophy and neurodegeneration. Whether autophagy may also be involved in neural development remains largely unclear. Here we report that <i>Mir505–3p</i> is a crucial regulator for axonal elongation and branching in vitro and in vivo, through modulating autophagy in neurons. We identify that the key target gene of <i>Mir505–3p</i> in neurons is <i>Atg12</i>, encoding ATG12 (autophagy-related 12) which is an essential component of the autophagy machinery during the initiation and expansion steps of autophagosome formation. Importantly, axonal development is compromised in brains of <i>mir505</i> knockout mice, in which autophagy signaling and formation of autophagosomes are consistently enhanced. These results define <i>Mir505–3p</i>-ATG12 as a vital signaling cascade for axonal development via the autophagy pathway, further suggesting the critical role of autophagy in neural development.