Next Article in Journal
Dynamic Tissue Rearrangements during Vertebrate Eye Morphogenesis: Insights from Fish Models
Next Article in Special Issue
Sonic Hedgehog Is a Member of the Hh/DD-Peptidase Family That Spans the Eukaryotic and Bacterial Domains of Life
Previous Article in Journal
The Biology of SUMO-Targeted Ubiquitin Ligases in Drosophila Development, Immunity, and Cancer
Previous Article in Special Issue
The Role of Hedgehog Signalling in the Formation of the Ventricular Septum
Open AccessReview

Taking the Occam’s Razor Approach to Hedgehog Lipidation and Its Role in Development

Institute of Physiological Chemistry and Pathobiochemistry and Cells-in-Motion Cluster of Excellence, University of Münster, D-48149 Münster, Germany
Author to whom correspondence should be addressed.
J. Dev. Biol. 2018, 6(1), 3;
Received: 5 January 2018 / Revised: 24 January 2018 / Accepted: 25 January 2018 / Published: 30 January 2018
(This article belongs to the Collection Hedgehog Signaling in Embryogenesis)
PDF [1206 KB, uploaded 30 January 2018]


All Hedgehog (Hh) proteins signal from producing cells to distant receiving cells despite being synthesized as N-and C-terminally lipidated, membrane-tethered molecules. To explain this paradoxical situation, over the past 15 years, several hypotheses have been postulated that tie directly into this property, such as Hh transport on cellular extensions called cytonemes or on secreted vesicles called lipophorins and exosomes. The alternative situation that tight membrane association merely serves to prevent unregulated Hh solubilization has been addressed by biochemical and structural studies suggesting Hh extraction from the membrane or proteolytic Hh release. While some of these models may act in different organisms, tissues or developmental programs, others may act together to specify Hh short- and long-range signaling in the same tissues. To test and rank these possibilities, we here review major models of Hh release and transport and hypothesize that the (bio)chemical and physical properties of firmly established, homologous, and functionally essential biochemical Hh modifications are adapted to specify and determine interdependent steps of Hh release, transport and signaling, while ruling out other steps. This is also described by the term “congruence”, meaning that the logical combination of biochemical Hh modifications can reveal their true functional implications. This combined approach reveals potential links between models of Hh release and transport that were previously regarded as unrelated, thereby expanding our view of how Hhs can steer development in a simple, yet extremely versatile, manner. View Full-Text
Keywords: Hedgehog; morphogen transport; posttranslational modification Hedgehog; morphogen transport; posttranslational modification

Figure 1

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

Share & Cite This Article

MDPI and ACS Style

Manikowski, D.; Kastl, P.; Grobe, K. Taking the Occam’s Razor Approach to Hedgehog Lipidation and Its Role in Development. J. Dev. Biol. 2018, 6, 3.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Related Articles

Article Metrics

Article Access Statistics



[Return to top]
J. Dev. Biol. EISSN 2221-3759 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top