PT - JOURNAL ARTICLE AU - Yao, Pamela J. AU - Petralia, Ronald S. AU - Ott, Carolyn AU - Wang, Ya-Xian AU - Lippincott-Schwartz, Jennifer AU - Mattson, Mark P. TI - Dendrosomatic Sonic Hedgehog Signaling in Hippocampal Neurons Regulates Axon Elongation AID - 10.1523/JNEUROSCI.1360-15.2015 DP - 2015 Dec 09 TA - The Journal of Neuroscience PG - 16126--16141 VI - 35 IP - 49 4099 - http://www.jneurosci.org/content/35/49/16126.short 4100 - http://www.jneurosci.org/content/35/49/16126.full SO - J. Neurosci.2015 Dec 09; 35 AB - The presence of Sonic Hedgehog (Shh) and its signaling components in the neurons of the hippocampus raises a question about what role the Shh signaling pathway may play in these neurons. We show here that activation of the Shh signaling pathway stimulates axon elongation in rat hippocampal neurons. This Shh-induced effect depends on the pathway transducer Smoothened (Smo) and the transcription factor Gli1. The axon itself does not respond directly to Shh; instead, the Shh signal transduction originates from the somatodendritic region of the neurons and occurs in neurons with and without detectable primary cilia. Upon Shh stimulation, Smo localization to dendrites increases significantly. Shh pathway activation results in increased levels of profilin1 (Pfn1), an actin-binding protein. Mutations in Pfn1's actin-binding sites or reduction of Pfn1 eliminate the Shh-induced axon elongation. These findings indicate that Shh can regulate axon growth, which may be critical for development of hippocampal neurons.SIGNIFICANCE STATEMENT Although numerous signaling mechanisms have been identified that act directly on axons to regulate their outgrowth, it is not known whether signals transduced in dendrites may also affect axon outgrowth. We describe here a transcellular signaling pathway in embryonic hippocampal neurons in which activation of Sonic Hedgehog (Shh) receptors in dendrites stimulates axon growth. The pathway involves the dendritic-membrane-associated Shh signal transducer Smoothened (Smo) and the transcription factor Gli, which induces the expression of the gene encoding the actin-binding protein profilin 1. Our findings suggest scenarios in which stimulation of Shh in dendrites results in accelerated outgrowth of the axon, which therefore reaches its presumptive postsynaptic target cell more quickly. By this mechanism, Shh may play critical roles in the development of hippocampal neuronal circuits.