Sonic hedgehog and BMP2 exert opposing actions on proliferation and differentiation of embryonic neural progenitor cells

Although Sonic Hedgehog (Shh) plays a critical role in brain development, i ts actions on neural progenitor cell proliferation and differentiation have not been clearly defined. Transcripts for the putative Shh-receptor genes patched (Ptc) and smoothened (Smo) are expressed by embryonic, postnatal, a nd adult progenitor cells, suggesting that Shh can act directly on these ce lls. The recombinant human amino-terminal fragment of Shh protein (Shh-N) a lone did not support the survival of cultured progenitor cells, but treatme nt with Shh-N in the presence of bFGF increased progenitor cell proliferati on. Furthermore, treatment of embryonic rat progenitor cells propagated eit her in primary culture or after mitogen expansion significantly increased t he proportions of both beta-tubulin- (neuronal marker) and O4- (oligodendro glial marker) immunoreactive cells and reduced the proportion of nestin- (u ncommitted neural progenitor cell marker) immunoreactive cells. By contrast Shh-N had no effect on the elaboration of GFAP- (astroglial marker) immuno reactive cells. Cotreatment with Shh-N and bone morphogenetic protein-2 (BM P2) inhibited the anti-proliferative, astroglial-inductive, and oligodendro glial-suppressive effects of BMP2. Our observations suggest that Shh-N sele ctively promotes the elaboration of both neuronal and oligodendroglial line age species and inhibits the effects of BMP2 on progenitor cell proliferati on and astroglial differentiation. (C) 1999 Academic Press.