Discrete localizations of hedgehog signalling components in the developing and adult rat nervous system.

Sonic hedgehog (Shh), a morphogen molecule implicated in embryonic tissue patterning, displays inductive, proliferative, neurotrophic and neuroprotective activities on various neural cells. Shh might exert its biological functions through binding to patched (Ptc) associated with smoothened (Smo), leading to downstream activation of target genes such as the transcription factor Gli1. We have performed a detailed localization of cells expressing transcripts of Shh, Ptc, Smo and Gli1 in brain and spinal cord of the adult rat as well as in the developing cerebellum. In the adult, Shh-positive cells were mainly observed in forebrain structures, in the Purkinje cells of the cerebellum and in motor neurons. Ptc-positive cells were frequently observed in brain areas devoid of any Shh transcripts, except in the median eminence 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 thalamic nucleus. The presence of Shh, Ptc and Smo transcripts in hypothalamic areas may indicate a role of Shh signalling in the modulation of neuroendocrine functions. The expression pattern of these three genes as well as of Gli1, and their developmental regulation in the cerebellum, suggest a possible role for Hedgehog signalling in the control of various cell populations within the cerebellum, particularly in granule cell proliferation and/or differentiation that might be impaired in proliferative states such as medulloblastomas.