High expression and anterograde axonal transport of aminoterminal sonic hedgehog in the adult hamster brain

Sonic hedgehog (SHH) is considered to play an important role in tissue indu ction and patterning during development, particularly in determining neuron al cell fate in the ventral neural tube and in the embryonic forebrain. SHH precursor is autoproteolytically cleaved to an aminoterminal fragment (SHH N) which retains all known SHH biological activities. Here, we demonstrate the expression of a 22-kDa SHHN immunoreactive peptide in developing and ad ult hamster brain regions using a rabbit antiserum directed against a mouse SHHN fragment. Interestingly, SHHN was developmentally regulated with the highest expression observed in the adult brain, was resistant to Triton X-1 00 solubilization at 4 degreesC and partitioned with the raft component gan glioside GM1 during density gradient centrifugation. In rat brain, Shh tran scripts were identified by double in situ hybridization in GABAergic neuron s located in various basal forebrain nuclei including globus pallidus, vent ral pallidum, medial septum-diagonal band complex, magnocellular preoptic n ucleus and in cerebellar Purkinje cells as well as in motoneurons of severa l cranial nerve nuclei and of the spinal cord. We show that radiolabelled S HHN peptides are synthesized in the adult hamster retina and are transporte d axonally along the optic nerve to the superior colliculus in vivo. Our da ta indicate that SHHN is associated with cholesterol rich raft-like microdo mains and anterogradely transported in the adult brain, and suggest that th e roles of this extracellular protein are more diverse than originally thou ght.