ArticlePLoS genetics2016
Craniofacial Ciliopathies Reveal Specific Requirements for GLI Proteins during Development of the Facial Midline.
Article in PLoS genetics, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 50 citations in OpenAlex.
- Primary cilia dysfunction: A critical driver of metabolic diseases (Review).International journal of molecular medicine · 2026Review
- Gli2 and Gli3 synergistically mediate HH-TGF-β crosstalk in mesenchymal progenitor cells to orchestrate tooth root morphogenesis.International journal of oral science · 2026Article
- A dual role for GLI3 signaling in neural crest development.Development (Cambridge, England) · 2026Article
- GPR161-GLI3 repressor signaling at cilia directs apical constriction and cell fate during cranial neural tube closure.Development (Cambridge, England) · 2025Article
- Loss of SPECC1L in cranial neural crest cells results in increased hedgehog signaling and frontonasal dysplasia.bioRxiv : the preprint server for biology · 2025Article
- Centriolar protein PIBF1 is required for craniofacial and forebrain development.Developmental biology · 2025Article
- Context-dependent ciliary regulation of hedgehog pathway repression in tissue morphogenesis.PLoS genetics · 2023Article
- Identification of a heterogeneous and dynamic ciliome during embryonic development and cell differentiation.Development (Cambridge, England) · 2023Article
- Short-term transcriptomic changes in the mouse neural tube induced by an acute alcohol exposure.Alcohol (Fayetteville, N.Y.) · 2023Article
- Non-cell-autonomous activation of hedgehog signaling contributes to disease progression in a mouse model of renal cystic ciliopathy.Human molecular genetics · 2022Article
- Article
- Prenatal alcohol exposure disrupts Sonic hedgehog pathway and primary cilia genes in the mouse neural tube.Reproductive toxicology (Elmsford, N.Y.) · 2021Article
- Ciliary and extraciliary Gpr161 pools repress hedgehog signaling in a tissue-specific manner.eLife · 2021Article
- Transcriptomic analyses of gastrulation-stage mouse embryos with differential susceptibility to alcohol.Disease models & mechanisms · 2021Article
- Thm2 interacts with paralog, Thm1, and sensitizes to Hedgehog signaling in postnatal skeletogenesis.Cellular and molecular life sciences : CMLS · 2021Article
- Mutation in the Ciliary Protein C2CD3 Reveals Organ-Specific Mechanisms of Hedgehog Signal Transduction in Avian Embryos.Journal of developmental biology · 2021Article
- Ciliopathic micrognathia is caused by aberrant skeletal differentiation and remodeling.Development (Cambridge, England) · 2021Article
- Developmental and regenerative paradigms of cilia regulated hedgehog signaling.Seminars in cell & developmental biology · 2021Review
- Gli3 utilizes Hand2 to synergistically regulate tissue-specific transcriptional networks.eLife · 2020Article
- Genetic interaction of mammalian IFT-A paralogs regulates cilia disassembly, ciliary entry of membrane protein, Hedgehog signaling, and embryogenesis.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2020Article
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4 authors at 1 institution in 1 country.
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Abstract
Ciliopathies represent a broad class of disorders that affect multiple organ systems. The craniofacial complex is among those most severely affected when primary cilia are not functional. We previously reported that loss of primary cilia on cranial neural crest cells, via a conditional knockout of the intraflagellar transport protein KIF3a, resulted in midfacial widening due to a gain of Hedgehog (HH) activity. Here, we examine the molecular mechanism of how a loss of primary cilia can produce facial phenotypes associated with a gain of HH function. We show that loss of intraflagellar transport proteins (KIF3a or IFT88) caused aberrant GLI processing such that the amount of GLI3FL and GLI2FL was increased, thus skewing the ratio of GLIFL to GLIR in favor of the FL isoform. Genetic addition of GLI3R partially rescued the ciliopathic midfacial widening. Interestingly, despite several previous studies suggesting midfacial development relies heavily on GLI3R activity, the conditional loss of GLI3 alone did not reproduce the ciliopathic phenotype. Only the combined loss of both GLI2 and GLI3 was able to phenocopy the ciliopathic midfacial appearance. Our findings suggest that ciliopathic facial phenotypes are generated via loss of both GLI3R and GLI2R and that this pathology occurs via a de-repression mechanism. Furthermore, these studies suggest a novel role for GLI2R in craniofacial development.
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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.