Hedgehog: functions and mechanisms

Varjosalo, Markku; Taipale, Jussi

doi:10.1101/gad.1693608

Cited by 1,217Hedgehog Signaling Pathway StudiesHippo pathway signaling and YAP/TAZGenetic and Kidney Cyst Diseases

Hedgehog: functions and mechanisms

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Varjosalo, Markku, Taipale, Jussi·2008·Genes & Development

DOI 10.1101/gad.1693608

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Abstract

The Hedgehog (Hh) family of proteins control cell growth, survival, and fate, and pattern almost every aspect of the vertebrate body plan. The use of a single morphogen for such a wide variety of functions is possible because cellular responses to Hh depend on the type of responding cell, the dose of Hh received, and the time cells are exposed to Hh. The Hh gradient is shaped by several proteins that are specifically required for Hh processing, secretion, and transport through tissues. The mechanism of cellular response, in turn, incorporates multiple feedback loops that fine-tune the level of signal sensed by the responding cells. Germline mutations that subtly affect Hh pathway activity are associated with developmental disorders, whereas somatic mutations activating the pathway have been linked to multiple forms of human cancer. This review focuses broadly on our current understanding of Hh signaling, from mechanisms of action to cellular and developmental functions. In addition, we review the role of Hh in the pathogenesis of human disease and the possibilities for therapeutic intervention.

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In mammals, the canonical Shh signaling pathway requires primary cilia.
“In mammals, this canonical Shh signaling pathway requires primary cilia [25, 29–34].”
From Amyloid-β interrupts canonical Sonic hedgehog signaling by distorting primary cilia structure (2018) · cites this paper as [25]
In “Divergence of pathway components and mechanisms” (page not supplied), the paper says mammalian Hh signaling depends on components involved in forming primary cilia. It also says those components might be needed for another microtubule-linked process and that whether ciliary localization is required remains unresolved. Thus, the source does not establish the categorical claim that the pathway requires primary cilia themselves. (LLM, conf=0.88)
Experimental — accuracy not yet measured
The canonical Shh signaling cascade relies on the primary cilium for signal transduction.
“The canonical Shh signaling cascade relies on the primary cilium for signal transduction [25, 29–34].”
From Amyloid-β interrupts canonical Sonic hedgehog signaling by distorting primary cilia structure (2018) · cites this paper as [25]
The “Divergence of pathway components and mechanisms” section says mammalian Hh signaling depends on components involved in forming primary cilia. It also explicitly says that whether localization to cilia is required for signaling remains to be established, so the categorical claim that the cascade relies on the primary cilium overstates the paper. Page numbers were not provided in our copy. (LLM, conf=0.88)
Experimental — accuracy not yet measured
The Sonic hedgehog (Shh) signaling pathway plays a pivotal role in development and neurogenesis.
“The Sonic hedgehog (Shh) signaling pathway is best known for its pivotal role in development and neurogenesis [23–28].”
From Amyloid-β interrupts canonical Sonic hedgehog signaling by distorting primary cilia structure (2018) · cites this paper as [25]
Shh showed highest expression in the notochord (cluster 30), together with Ntn1, Slit1, and Spon1.
“we detect the highest expression of sonic hedgehog (Shh)28 in the notochord (cluster 30), together with Ntn1, Slit1, and Spon1”
From The single-cell transcriptional landscape of mammalian organogenesis (2019) · cites this paper as [28]

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Authors: Varjosalo, M., & Taipale, J.
Affiliations: University of Helsinki (FI)
ORCID: Varjosalo, Markku
Taipale, Jussi
Venue: Genes & Development
Publisher: Cold Spring Harbor Laboratory
Published: 2008-09-15
Volume: 22
Issue: 18
Pages: 2454-2472
ISSN: 0890-9369 (ISSN-L)
1549-5477
DOI: 10.1101/gad.1693608
OpenAlex: W2107394975
Cited by: 1,217
References: 271
Citations by year: 2026: 8 · 2025: 25 · 2024: 36 · 2023: 50 · 2022: 61 · 2021: 87 · 2020: 77 · 2019: 80 · 2018: 87 · 2017: 84 · 2016: 75 · 2015: 104 · 2014: 72 · 2013: 72 · 2012: 75
Type: posted content
Language: en
Open access: hybrid
doi.org
Licence: other-oa
Locations: Genes & Development (publishedVersion, other-oa)
PubMed (publishedVersion)
HighWire Press Open Archive (submittedVersion)
Funders: Academy of Finland
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Hedgehog Signaling Pathway Studies
Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Hippo pathway signaling and YAP/TAZ
Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic and Kidney Cyst Diseases
Keywords: Hedgehog signaling, Hedgehog proteins, morphogen gradients, cell fate specification, cell growth and survival, feedback loops, germline mutations, developmental disorders, somatic mutations, cancer, therapeutic interventions
MeSH terms: Animals, Cell Division, Cell Survival, Humans, Cell Lineage, Body Patterning, Hedgehog Proteins

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