Sonic hedgehog (Shh) regulates neural progenitor cells in the adult brain but its role in postmitotic mature neurons is not well understood. Using immunoelectron microscopy, we have recently demonstrated the postsynaptic distribution of Patched (Ptch) and Smoothened (Smo), the receptors for Shh, in hippocampal neurons of the adult rat brain. In this study, we describe the distribution of Shh protein in these adult hippocampal neurons. We find that Shh is present in both presynaptic and postsynaptic terminals. In presynaptic terminals, Shh is located either at the center or on the side of the synaptic junction. In postsynaptic terminals, Shh is mostly located on the side of the synaptic junction. We also find Shh in dendrites. Synaptic and dendritic Shh often reside in or are associated with vesicular structures that include dense-cored vesicles, synaptic vesicles, and endosomes. Thus, our subcellular map of Shh and its receptors provides a foundation for elucidating the functional significance of Shh signaling in mature neurons.
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