Nature Neuroscience
3, 41 - 46 (2000)
doi:10.1038/71114
The seven-transmembrane receptor Smoothened cell-autonomously induces
multiple ventral cell typesMary Hynes1, Weilan Ye1, Kevin Wang1, Donna Stone1, Maximilien Murone2, Frederic de Sauvage2
& Arnon Rosenthal11
Department of Neuroscience, Genentech, Inc.,
South San Francisco, California 94080, USA
2
Department of Molecular Oncology, Genentech, Inc.,
South San Francisco, California 94080, USA
Correspondence should be addressed to Mary Hynes mah@gene.com or Arnon Rosenthal ar@gene.comSonic Hedgehog (Shh) is a secreted protein that controls cell fate and
mitogenesis in the developing nervous system. Here we show that a constitutively
active form of Smoothened (Smo-M2) mimics concentration-dependent actions
of Shh in the developing neural tube, including activation of ventral marker
genes (HNF3 , patched, Nkx2.2, netrin-1),
suppression of dorsal markers (Pax-3, Gli-3, Ephrin A5)
and induction of ventral neurons (dopaminergic, serotonergic) and ventrolateral
motor neurons (Islet-1+, Islet-2+, HB9+) and interneurons (Engrailed-1+, CHX10+).
Furthermore, Smo-M2's patterning activities were cell autonomous, occurring
exclusively in cells expressing Smo-M2. These findings suggest that
Smo is a key signaling component in the Hh receptor and that Shh patterns
the vertebrate nervous system as a morphogen, rather than through secondary
relay signals.
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