The seven-transmembrane receptor Smoothened cell-autonomously induces multiple ventral cell types
Copyright policy )The seven-transmembrane receptor Smoothened cell-autonomously induces multiple ventral cell types
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 (HNF3beta, 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.
- GENENTECH INC United States
Embryonic Induction, Motor Neurons, Brain, Gene Expression Regulation, Developmental, Proteins, Mice, Transgenic, Receptors, Cell Surface, Chick Embryo, Embryo, Mammalian, Antigens, Differentiation, Receptors, G-Protein-Coupled, Mice, Homeobox Protein Nkx-2.2, Amino Acid Substitution, Genes, Reporter, Interneurons, Neural Crest, Animals, Hedgehog Proteins, Body Patterning
Embryonic Induction, Motor Neurons, Brain, Gene Expression Regulation, Developmental, Proteins, Mice, Transgenic, Receptors, Cell Surface, Chick Embryo, Embryo, Mammalian, Antigens, Differentiation, Receptors, G-Protein-Coupled, Mice, Homeobox Protein Nkx-2.2, Amino Acid Substitution, Genes, Reporter, Interneurons, Neural Crest, Animals, Hedgehog Proteins, Body Patterning
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