Rab23 is an essential negative regulator of the mouse Sonic hedgehog signalling pathway.
The mouse open brain (opb) and Sonic hedgehog (Shh) genes have opposing roles in neural patterning: opb is required for dorsal cell types and Shh is required for ventral cell types in the spinal cord. Here we show that opb acts downstream of Shh. Ventral cell types that are absent in Shh mutants, including the floor plate, are present in Shh opb double mutants. The organization of ventral cell types in Shh opb double mutants reveals that Shh-independent mechanisms can pattern the neural tube along its dorsal-ventral axis. We cloned opb by a map-based approach and found that it encodes Rab23, a member of the Rab family of vesicle transport proteins. The data indicate that dorsalizing signals activate transcription of Rab23 in order to silence the Shh pathway in dorsal neural cells.
Eggenschwiler
J T
JT
Molecular Biology Program, Sloan-Kettering Institute, New York, New York 10021, USA.
Espinoza
E
E
Anderson
K V
KV
D000595:Amino Acid Sequence; D000818:Animals; D019521:Body Patterning; D019485:Bone Morphogenetic Proteins / Q000378:metabolism; D002874:Chromosome Mapping; D004330:Drosophila; D053823:Hedgehog Proteins; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D008809:Mice, Inbred C3H; D008969:Molecular Sequence Data; D009154:Mutation; D009420:Nervous System / Q000196:embryology / Q000378:metabolism*; D000072079:Patched Receptors; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D011956:Receptors, Cell Surface; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction; D013116:Spinal Cord / Q000196:embryology / Q000378:metabolism; D015534:Trans-Activators; D020691:rab GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*
D019485:Bone Morphogenetic Proteins; D053823:Hedgehog Proteins; D008565:Membrane Proteins; D000072079:Patched Receptors; D011506:Proteins; D011956:Receptors, Cell Surface; C509239:SHH protein, human; D015534:Trans-Activators; C486614:RAB23 protein, human; C431746:Rab23 protein, mouse; D020691:rab GTP-Binding Proteins