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.
Hynes
M
M
Department of Neuroscience, Genentech, Inc., South San Francisco, California 94080, USA. mah@gene.com
Ye
W
W
Wang
K
K
Stone
D
D
Murone
M
M
Sauvage
F d
Fd
Rosenthal
A
A
D019943:Amino Acid Substitution; D000818:Animals; D000943:Antigens, Differentiation / Q000378:metabolism; D019521:Body Patterning / Q000235:genetics / Q000502:physiology*; D001921:Brain / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D002642:Chick Embryo; D004622:Embryo, Mammalian; D004627:Embryonic Induction; D018507:Gene Expression Regulation, Developmental; D017930:Genes, Reporter; D053823:Hedgehog Proteins; D000090322:Homeobox Protein Nkx-2.2; D007395:Interneurons / Q000166:cytology / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D009046:Motor Neurons / Q000166:cytology / Q000378:metabolism; D009432:Neural Crest / Q000166:cytology / Q000196:embryology* / Q000378:metabolism; D011506:Proteins / Q000502:physiology; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D043562:Receptors, G-Protein-Coupled; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology*; D000072086:Smoothened Receptor; D013116:Spinal Cord / Q000166:cytology / Q000196:embryology; D015534:Trans-Activators; D014162:Transfection
D000943:Antigens, Differentiation; D053823:Hedgehog Proteins; D000090322:Homeobox Protein Nkx-2.2; C000715627:Nkx2-2 protein, mouse; D011506:Proteins; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; C491022:Smo protein, mouse; D000072086:Smoothened Receptor; D015534:Trans-Activators