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The seven-transmembrane receptor Smoothened cell-autonomously induces multiple ventral cell types
- Mary Hynes1,
- Weilan Ye1,
- Kevin Wang1,
- Donna Stone1,
- Maximilien Murone2,
- Frederic de Sauvage2 &
- …
- Arnon Rosenthal1
Nature Neurosciencevolume 3, pages41–46 (2000)Cite this article
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Abstract
Sonic 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 (HNF3β,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 expressingSmo-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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Acknowledgements
We thank Kenji Shimamura for help with the electroporation, Susan Brenner-Morton and T. Jessell for the Islet-1, En-1, Chx-10 and HB9 antibodies and A. Ruiz i Altaba for the HNF-3β antiserum. We also thank E. Berry and A. Bruce for help with preparation of the manuscript and A. Shih and K. Poulsen for technical assistance.
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Department of Neuroscience, Genentech, Inc., South San Francisco, 94080, California, USA
Mary Hynes, Weilan Ye, Kevin Wang, Donna Stone & Arnon Rosenthal
Department of Molecular Oncology, Genentech, Inc., South San Francisco, 94080, California, USA
Maximilien Murone & Frederic de Sauvage
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- Weilan Ye
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- Maximilien Murone
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- Frederic de Sauvage
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- Arnon Rosenthal
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Hynes, M., Ye, W., Wang, K.et al. The seven-transmembrane receptor Smoothened cell-autonomously induces multiple ventral cell types.Nat Neurosci3, 41–46 (2000). https://doi.org/10.1038/71114
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