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Rab23 is an essential negative regulator of the mouse Sonic hedgehog signalling pathway

Abstract

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 cord1,2,3. 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.

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Figure 1: The opb mutation rescues the Shh mutant phenotype.
Figure 2: Patched1–lacZ expression in E9.5 embryos.
Figure 3: Neural patterning in Shhopb2 mutants.
Figure 4: Molecular identification of opb.
Figure 5: Rab23 expression in E10.5 embryos.

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Acknowledgements

Monoclonal antibodies were obtained from the Developmental Studies Hybridoma Bank developed under the auspices of the NICHD and maintained by The University of Iowa, Department of Biological Sciences. We thank P. Beachy and M. Scott for discussions and for gifts of the Shh mice and Patched–lacZ mice; M. Rosen for discussions about Rab structure; and M. J. García-García, K. Brennan, J. Timmer, L. Niswander and T. Bestor for helpful comments on the manuscript. This work was supported by an NIH grant (K.V.A.), the Lita Annenberg Hazen Foundation and an ACS postdoctoral fellowship to J.T.E.

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Correspondence to Kathryn V. Anderson.

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Eggenschwiler, J., Espinoza, E. & Anderson, K. Rab23 is an essential negative regulator of the mouse Sonic hedgehog signalling pathway. Nature 412, 194–198 (2001). https://doi.org/10.1038/35084089

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