ArticlePLoS genetics2018
FoxO6 regulates Hippo signaling and growth of the craniofacial complex.
Article in PLoS genetics, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 35 citations in OpenAlex.
- Forkhead box O proteins in chondrocyte aging and diseases.Journal of orthopaedic translation · 2025Review
- Addressing osteoblast senescence: Molecular pathways and the frontier of anti-ageing treatments.Clinical and translational medicine · 2025Review
- Modelling quiescence exit of neural stem cells reveals a FOXG1-FOXO6 axis.Disease models & mechanisms · 2024Article
- The Hippo signalling pathway in bone homeostasis: Under the regulation of mechanics and aging.Cell proliferation · 2024Review
- A screen for regeneration-associated silencer regulatory elements in zebrafish.Developmental cell · 2024Article
- Reproductive biology of the "Brazilian pine" (Araucaria angustifolia-Araucariaceae): the pollen tube growth and the seed cone development.Plant reproduction · 2024Article
- FOXO family isoforms.Cell death & disease · 2023Review
- A comprehensive review of stroke-related signaling pathways and treatment in western medicine and traditional Chinese medicine.Frontiers in neuroscience · 2023Review
- Distinct and overlapping functions of YAP and TAZ in tooth development and periodontal homeostasis.Frontiers in cell and developmental biology · 2023Review
- LATS1/2 control TGFB-directed epithelial-to-mesenchymal transition in the murine dorsal cranial neuroepithelium through YAP regulation.Development (Cambridge, England) · 2022Article
- Annotating functional effects of non-coding variants in neuropsychiatric cell types by deep transfer learning.PLoS computational biology · 2022Article
- Gene regulatory network from cranial neural crest cells to osteoblast differentiation and calvarial bone development.Cellular and molecular life sciences : CMLS · 2022Review
- Elucidating the Possible Role of FoxO in Depression.Neurochemical research · 2021Review
- Duration of the pubertal growth spurt in patients with increased craniofacial growth component in sagittal and vertical planes-retrospective and cross-sectional study.Clinical oral investigations · 2021Article
- The miR-200 family is required for ectodermal organ development through the regulation of the epithelial stem cell niche.Stem cells (Dayton, Ohio) · 2021Article
- The Hippo pathway: Horizons for innovative treatments of peripheral nerve diseases.Journal of the peripheral nervous system : JPNS · 2021Review
- Review
- Notch signaling: Its essential roles in bone and craniofacial development.Genes & diseases · 2021Review
- DNA Methylation Variation Is Identified in Monozygotic Twins Discordant for Non-syndromic Cleft Lip and Palate.Frontiers in cell and developmental biology · 2021Article
- A developmental stage-specific network approach for studying dynamic co-regulation of transcription factors and microRNAs during craniofacial development.Development (Cambridge, England) · 2020Article
Corrections and comments
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Authors and funding
17 authors at 4 institutions in 1 country.
Funding
Abstract
The mechanisms that regulate post-natal growth of the craniofacial complex and that ultimately determine the size and shape of our faces are not well understood. Hippo signaling is a general mechanism to control tissue growth and organ size, and although it is known that Hippo signaling functions in neural crest specification and patterning during embryogenesis and before birth, its specific role in postnatal craniofacial growth remains elusive. We have identified the transcription factor FoxO6 as an activator of Hippo signaling regulating neonatal growth of the face. During late stages of mouse development, FoxO6 is expressed specifically in craniofacial tissues and FoxO6-/- mice undergo expansion of the face, frontal cortex, olfactory component and skull. Enlargement of the mandible and maxilla and lengthening of the incisors in FoxO6-/- mice are associated with increases in cell proliferation. In vitro and in vivo studies demonstrated that FoxO6 activates Lats1 expression, thereby increasing Yap phosphorylation and activation of Hippo signaling. FoxO6-/- mice have significantly reduced Hippo Signaling caused by a decrease in Lats1 expression and decreases in Shh and Runx2 expression, suggesting that Shh and Runx2 are also linked to Hippo signaling. In vitro, FoxO6 activates Hippo reporter constructs and regulates cell proliferation. Furthermore PITX2, a regulator of Hippo signaling is associated with Axenfeld-Rieger Syndrome causing a flattened midface and we show that PITX2 activates FoxO6 expression. Craniofacial specific expression of FoxO6 postnatally regulates Hippo signaling and cell proliferation. Together, these results identify a FoxO6-Hippo regulatory pathway that controls skull growth, odontogenesis and face morphology.
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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.