An ancient yet flexible cis-regulatory architecture allows localized Hedgehog tuning by patched/Ptch1
- University of Michigan Medical School, United States
- Harvard University, United States
- National Institutes of Health, United States
- University of Southern California Keck School of Medicine, United States
- Keck School of Medicine of the University of Southern California, United States
Abstract
The Hedgehog signaling pathway is part of the ancient developmental-evolutionary animal toolkit. Frequently co-opted to pattern new structures, the pathway is conserved among eumetazoans yet flexible and pleiotropic in its effects. The Hedgehog receptor, Patched, is transcriptionally activated by Hedgehog, providing essential negative feedback in all tissues. Our locus-wide dissections of the cis-regulatory landscapes of fly patched and mouse Ptch1 reveal abundant, diverse enhancers with stage- and tissue-specific expression patterns. The seemingly simple, constitutive Hedgehog response of patched/Ptch1 is driven by a complex regulatory architecture, with batteries of context-specific enhancers engaged in promoter-specific interactions to tune signaling individually in each tissue, without disturbing patterning elsewhere. This structure-one of the oldest cis-regulatory features discovered in animal genomes-explains how patched/Ptch1 can drive dramatic adaptations in animal morphology while maintaining its essential core function. It may also suggest a general model for the evolutionary flexibility of conserved regulators and pathways.
Article and author information
Author details
Ethics
Animal experimentation: This study was performed in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health, and with the institutional animal care protocols of Harvard University and The Jackson Laboratories, where the animal experimentation was performed.Animal husbandry and all experiments were performed in accordance with the National Institute of Health guidelines and the Institutional Animal Care and Use Committee of the University of Southern California (protocol #11867).
Copyright
This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.
Metrics
-
- 3,147
- views
-
- 662
- downloads
-
- 39
- citations
Views, downloads and citations are aggregated across all versions of this paper published by eLife.
Download links
A two-part list of links to download the article, or parts of the article, in various formats.
Downloads (link to download the article as PDF)
Open citations (links to open the citations from this article in various online reference manager services)
Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)
An ancient yet flexible cis-regulatory architecture allows localized Hedgehog tuning by patched/Ptch1
eLife 5:e13550.
https://doi.org/10.7554/eLife.13550
Further reading
-
- Developmental Biology
Proteins that allow water to move in and out of cells help shape the development of new blood vessels.
-
- Developmental Biology
- Neuroscience
The ligand Netrin mediates axon guidance through a combination of haptotaxis over short distances and chemotaxis over longer distances.
