Sonic hedgehog (Shh) signalling is one of the key pathways that promote ventral cell fate identity in the developing neural tube. Whereas some cells strictly require high levels of Shh activity for ventral specification, others can be specified by intermediate or low Shh activity levels over time. Now, Tamara Caspary and co-workers investigate the role of Inpp5e, a ciliary inositol polyphosphate-5-phosphatase that is thought to positively regulate Shh signalling, in allowing cells to sense the duration of Shh signalling. They find that a null mutant of Inpp5e (Inpp5erdg/rdg) shows an expansion of ventral cell fates by E10.5, suggesting that Inpp5e negatively regulates the Shh response. Yet ventral patterning in Inpp5erdg/rdg embryos recovers by E12.5, and this depends on the presence of Gli3, a repressor of Shh signalling. However, in mutants of the Shh activator smoothened, the Inpp5erdg/rdg mutation only rescues the expression of markers that are induced by intermediate levels of Shh, but not the expression of those that require high Shh concentrations. Therefore, Inpp5e is not simply a negative regulator of Shh. Additionally, Inpp5e loss promotes inhibitors of Shh signalling to associate with cilia, thus confirming its previously known roles in promoting the Shh response. Collectively, these results indicate that Inpp5e acts as both a positive and negative regulator of Shh function, and attenuates Shh signalling to prevent the untimely expression of ventral specification factors.
Attenuation, please! Inpp5e as a timer of sonic hedgehog signalling
- Split-screen
- Views Icon Views
-
Article Versions Icon
Versions
- Version of Record 03 February 2020
- Share Icon Share
-
Tools Icon
Tools
- Search Site
Attenuation, please! Inpp5e as a timer of sonic hedgehog signalling. Development 1 February 2020; 147 (3): e0302. doi:
Download citation file:
Advertisement
Cited by
About us

Our publisher, The Company of Biologists, turns 100 this year. Read about the history of the Company and find out what Sarah Bray, our Chair of the Board of Directors, has to say.
Biologists @ 100 - join us in Liverpool in March 2025

We are excited to invite you to a unique scientific conference, celebrating the 100-year anniversary of The Company of Biologists, and bringing together our different communities. The conference will incorporate the Spring Meetings of the BSCB and the BSDB, the JEB Symposium Sensory Perception in a Changing World and a DMM programme on antimicrobial resistance. Find out more and register by 28 February 2025 to join us in March 2025 in Liverpool, UK.
Call for papers – Lifelong Development: the Maintenance, Regeneration and Plasticity of Tissues

Development invites you to submit your latest research to our upcoming special issue – Lifelong Development: the Maintenance, Regeneration and Plasticity of Tissues. This issue will be coordinated by Guest Editors Meritxell Huch (Max Planck Institute of Molecular Cell Biology and Genetics, Germany) and Mansi Srivastava (Harvard University and Museum of Comparative Zoology, USA), working alongside our team of academic Editors. Submit your articles by 15 May 2025.
A case for broadening our view of mechanism in developmental biology

In this Perspective, B. Duygu Özpolat and colleagues survey researchers on their views on what it takes to infer mechanism in developmental biology. They examine what factors shape our idea of what we mean by ‘mechanism’ and suggest a path forward that embraces a broad outlook on the diversity of studies that advance knowledge in our field.
In preprints
Did you know that Development publishes perspectives on recent preprints? These articles help our readers navigate the ever-growing preprint literature. We welcome proposals for ‘In preprints’ articles, so please do get in touch if you’d like to contribute.