Sonic hedgehog promotes autophagy in hippocampal neurons.

The Sonic hedgehog (Shh) signaling pathway is well known in patterning of the neural tube during embryonic development, but its emerging role in differentiated neurons is less understood. Here we report that Shh enhances autophagy in cultured hippocampal neurons. Microarray analysis reveals the upregulation of multiple autophagy-related genes in neurons in response to Shh application. Through analysis of the autophagy-marker LC3 by immunoblot analysis and immunocytochemistry, we confirm activation of the autophagy pathway in Shh-exposed neurons. Using electron microscopy, we find autophagosomes and associated structures with a wide range of morphologies in synaptic terminals of Shh-exposed neurons. Moreover, we show that Shh-triggered autophagy depends on class III Phosphatidylinositol 3-kinase complexes (PtdIns3K). These results identify a link between Shh and autophagy pathways and, importantly, provide a lead for further understanding the physiology of Shh signaling activity in neurons.