ArticleDevelopmental dynamics : an official publication of the American Association of Anatomists2012
Signaling by SHH rescues facial defects following blockade in the brain.
Article in Developmental dynamics : an official publication of the American Association of Anatomists, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 50 citations in OpenAlex.
- Navigating the window: structural bottlenecks in avian craniofacial integration revealed by the ontogenetic patterning of shape variance.bioRxiv : the preprint server for biology · 2026Article
- PBX1 and PBX3 transcription factors regulate SHH expression in the Frontonasal Ectodermal Zone through complementary mechanisms.PLoS genetics · 2025Article
- Sonic hedgehog and fibroblast growth factor 8 regulate the evolution of amniote facial proportions.Communications biology · 2025Article
- A Novel Perspective on Neuronal Control of Anatomical Patterning, Remodeling, and Maintenance.International journal of molecular sciences · 2023Review
- Characterization of SHH, SOX3, WNT3A and WNT9B Proteins in Human Non-Syndromic Cleft Lip and Palate Tissue.Dentistry journal · 2023Article
- Shared heritability of human face and brain shape.Nature genetics · 2021Article
- Environmental Thermal Stress Induces Neuronal Cell Death and Developmental Malformations in Reptiles.Integrative organismal biology (Oxford, England) · 2021Article
- Article
- miR-199 family contributes to regulation of sonic hedgehog expression during craniofacial development.Developmental dynamics : an official publication of the American Association of Anatomists · 2020Article
- Molecular and cellular mechanisms underlying the evolution of form and function in the amniote jaw.EvoDevo · 2019Review
- Signals from the brain and olfactory epithelium control shaping of the mammalian nasal capsule cartilage.eLife · 2018Article
- Neural crest and the origin of species-specific pattern.Genesis (New York, N.Y. : 2000) · 2018Review
- Neural crest cells utilize primary cilia to regulate ventral forebrain morphogenesis via Hedgehog-dependent regulation of oriented cell division.Developmental biology · 2017Article
- Discovery, Diagnosis, and Etiology of Craniofacial Ciliopathies.Cold Spring Harbor perspectives in biology · 2017Review
- Oriented clonal cell dynamics enables accurate growth and shaping of vertebrate cartilage.eLife · 2017Article
- Craniofacial Ciliopathies Reveal Specific Requirements for GLI Proteins during Development of the Facial Midline.PLoS genetics · 2016Article
- Utilizing the chicken as an animal model for human craniofacial ciliopathies.Developmental biology · 2016Review
- Genetics of murine craniofacial morphology: diallel analysis of the eight founders of the Collaborative Cross.Journal of anatomy · 2016Article
- The Nervous System Orchestrates and Integrates Craniofacial Development: A Review.Frontiers in physiology · 2016Review
- Correlations Between the Morphology of Sonic Hedgehog Expression Domains and Embryonic Craniofacial Shape.Evolutionary biology · 2015Article
Corrections and comments
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Authors and funding
7 authors at 4 institutions in 2 countries.
Funding
Abstract
backgroundThe Frontonasal Ectodermal Zone (FEZ) is a signaling center in the face that expresses Sonic hedgehog (Shh) and regulates patterned growth of the upper jaw. Blocking SHH in the forebrain blocks Shh expression in the FEZ and creates malformations resembling holoprosencephaly (HPE), while inhibition of BMP signaling in the mesenchyme blocks FEZ formation and causes similar dysmorphology. Thus, the brain could regulate FEZ formation by SHH or BMP signaling, and if so, activating one of these pathways in the face might alleviate the effects of repression of SHH in the brain.
resultsWe blocked SHH signaling in the brain while adding SHH or BMP between the neural and facial ectoderm of the frontonasal process. When applied early, SHH restored Shh expression in the FEZ and significantly improved shape outcomes, which contrasts with our previous experiments that showed later SHH treatments have no effect. BMP-soaked beads introduced early and late caused apoptosis that exacerbated malformations. Finally, removal of Smoothened from neural crest cells did not inhibit Shh expression in the FEZ.
conclusionsCollectively, this work suggests that a direct, time-sensitive SHH signal from the brain is required for the later induction of Shh in the FEZ. We propose a testable model of FEZ activation and discuss signaling mediators that may regulate these interactions.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.