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The seven-transmembrane receptor Smoothened cell-autonomously induces multiple ventral cell types

Nature Neuroscience volume 3, pages 41–46 (2000)Cite this article

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 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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Figure 1: Smo-M2 ventralizes the neural tube in transgenic mice.
Figure 2: Induction of multiple neuronal classes and netrin-1, in Smo-M2 TG mice.
Figure 3: Changes in gene expression in the midbrain/hindbrain region are confined to the Smo-M2 expression domain.
Figure 4: Smo-M2 induces Islet-1+ motor neurons cell autonomously in the mid/hindbrain region.
Figure 5: Smo-M2 induces ventral and ventrolateral markers and cell types in the spinal cord.

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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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Authors and Affiliations

  1. Department of Neuroscience, Genentech, Inc., South San Francisco, 94080, California, USA

    Mary Hynes, Weilan Ye, Kevin Wang, Donna Stone & Arnon Rosenthal

  2. Department of Molecular Oncology, Genentech, Inc., South San Francisco, 94080, California, USA

    Maximilien Murone & Frederic de Sauvage

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  1. Mary Hynes
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Correspondence to Mary Hynes or 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 Neurosci 3, 41–46 (2000). https://doi.org/10.1038/71114

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