Discrete localizations of hedgehog signalling components in the developingand adult rat nervous system

Sonic hedgehog (Shh), a morphogen molecule implicated in embryonic tissue p atterning, displays inductive, proliferative, neurotrophic and neuroprotect ive activities on various neural cells. Shh might exert its biological func tions through binding to patched (Ptc) associated with smoothened (Smo), le ading to downstream activation of target genes such as the transcription fa ctor Gli1. We have performed a detailed localization of cells expressing tr anscripts of Shh, Ptc, Smo and Gli1 in brain and spinal cord of the adult r at as well as in the developing cerebellum. In the adult, Shh-positive cell s were mainly observed in forebrain structures, in the Purkinje cells of th e cerebellum and in motor neurons. Ptc-positive cells were frequently obser ved in brain areas devoid of any Shh transcripts, except in the median emin ence or the facial nucleus, suggesting local Shh signalling. Interestingly, Smo transcripts were predominantly present within circumventricular organs , in granular cells of the dentate gyrus and in neurons of the reticular th alamic nucleus. The presence of Shh, Ptc and Smo transcripts in hypothalami c areas may indicate a role of Shh signalling in the modulation of neuroend ocrine functions. The expression pattern of these three genes as well as of Gli1, and their developmental regulation in the cerebellum, suggest a poss ible role for Hedgehog signalling in the control of various cell population s within the cerebellum, particularly in granule cell proliferation and/or differentiation that might be impaired in proliferative states such as medu lloblastomas.