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Rab23 is an essential negative regulator of the mouse Sonic hedgehog signalling pathway
J T Eggenschwiler1, E Espinoza, K V Anderson
1Molecular Biology Program, Sloan-Kettering Institute, New York, New York 10021, USA.
Nature
|July 13, 2001
Summary
The mouse open brain (opb) gene, Rab23, acts downstream of Sonic hedgehog (Shh) to regulate spinal cord development. This reveals Shh-independent mechanisms in neural tube patterning.
Area of Science:
- Developmental Biology
- Neuroscience
- Genetics
Background:
- The mouse open brain (opb) and Sonic hedgehog (Shh) genes play opposing roles in spinal cord neural patterning.
- opb is essential for dorsal cell types, while Shh is crucial for ventral cell types.
Purpose of the Study:
- To investigate the relationship between opb and Shh in neural patterning.
- To identify the molecular identity and function of the opb gene.
Main Methods:
- Map-based cloning to identify the opb gene.
- Analysis of Shh and Shh opb double mutant mice to study neural patterning.
- Investigating the role of Rab23 in the Shh signaling pathway.
Main Results:
- The opb gene encodes Rab23, a vesicle transport protein.
- opb acts downstream of Shh in spinal cord development.
- Ventral cell types, including the floor plate, are present in Shh opb double mutants, indicating Shh-independent patterning mechanisms.
- Dorsalizing signals activate Rab23 transcription to inhibit the Shh pathway in dorsal neural cells.
Conclusions:
- Rab23 (opb) functions downstream of Shh to regulate ventral neural cell fates.
- Shh-independent mechanisms contribute to the dorsal-ventral patterning of the neural tube.
- The Shh pathway is regulated by dorsalizing signals through Rab23.
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