ArticleDevelopmental biology2011
The canonical Wnt signaling activator, R-spondin2, regulates craniofacial patterning and morphogenesis within the branchial arch through ectodermal-mesenchymal interaction.
Article in Developmental biology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.
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Who cites it
47 citing papers in PubMed, 78 citations in OpenAlex.
- Gene expression dynamics of human and mouse craniofacial development at the single-cell level.Nature communications · 2026Article
- Article
- R-spondin 2 suppresses hepatic steatosis via activation of AMPK-ACC signaling.JHEP reports : innovation in hepatology · 2025Article
- RSPO2 as Wnt signaling enabler: Important roles in cancer development and therapeutic opportunities.Genes & diseases · 2024Review
- Endothelin signaling in development.Development (Cambridge, England) · 2023Review
- LGR4: A New Receptor Member in Endocrine and Metabolic Diseases.Endocrine reviews · 2023Review
- The biological functions and related signaling pathways of SPON2.Frontiers in oncology · 2023Review
- Understanding the development of oral epithelial organs through single cell transcriptomic analysis.Development (Cambridge, England) · 2022Article
- Candidate positive targets of LHX6 and LHX8 transcription factors in the developing upper jaw.Gene expression patterns : GEP · 2022Article
- R-Spondin 3 Regulates Mammalian Dental and Craniofacial Development.Journal of developmental biology · 2021Article
- Wnt-Dependent Activation of ERK Mediates Repression of Chondrocyte Fate during Calvarial Development.Journal of developmental biology · 2021Article
- Transcriptomic changes due to early, chronic intermittent alcohol exposure during forebrain development implicate WNT signaling, cell-type specification, and cortical regionalization as primary determinants of fetal alcohol syndrome.Alcoholism, clinical and experimental research · 2021Article
- Identification of Novel Variants in Cleft Palate-Associated Genes in Brazilian Patients With Non-syndromic Cleft Palate Only.Frontiers in cell and developmental biology · 2021Article
- Genetics and signaling mechanisms of orofacial clefts.Birth defects research · 2020Review
- R-spondin 2 mediates neutrophil egress into the alveolar space through increased lung permeability.BMC research notes · 2020Article
- Canonical WNT/β-Catenin Signaling Activated by WNT9b and RSPO2 Cooperation Regulates Facial Morphogenesis in Mice.Frontiers in cell and developmental biology · 2020Article
- Pointing on the early stages of maxillary bone and tooth development - histological findings.Romanian journal of morphology and embryology = Revue roumaine de morphologie et embryologie · 2020Article
- WNT Signaling and Bone: Lessons From Skeletal Dysplasias and Disorders.Frontiers in endocrinology · 2020Review
- MicroRNA-124-3p suppresses mouse lip mesenchymal cell proliferation through the regulation of genes associated with cleft lip in the mouse.BMC genomics · 2019Article
- R-spondin signaling as a pivotal regulator of tissue development and homeostasis.The Japanese dental science review · 2019Review
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
R-spondins are a recently characterized family of secreted proteins that activate Wnt/β-catenin signaling. Herein, we determine R-spondin2 (Rspo2) function in craniofacial development in mice. Mice lacking a functional Rspo2 gene exhibit craniofacial abnormalities such as mandibular hypoplasia, maxillary and mandibular skeletal deformation, and cleft palate. We found that loss of the mouse Rspo2 gene significantly disrupted Wnt/β-catenin signaling and gene expression within the first branchial arch (BA1). Rspo2, which is normally expressed in BA1 mesenchymal cells, regulates gene expression through a unique ectoderm-mesenchyme interaction loop. The Rspo2 protein, potentially in combination with ectoderm-derived Wnt ligands, up-regulates Msx1 and Msx2 expression within mesenchymal cells. In contrast, Rspo2 regulates expression of the Dlx5, Dlx6, and Hand2 genes in mesenchymal cells via inducing expression of their upstream activator, Endothelin1 (Edn1), within ectodermal cells. Loss of Rspo2 also causes increased cell apoptosis, especially within the aboral (or caudal) domain of the BA1, resulting in hypoplasia of the BA1. Severely reduced expression of Fgf8, a survival factor for mesenchymal cells, in the ectoderm of Rspo2(-/-) embryos is likely responsible for increased cell apoptosis. Additionally, we found that the cleft palate in Rspo2(-/-) mice is not associated with defects intrinsic to the palatal shelves. A possible cause of cleft palate is a delay of proper palatal shelf elevation that may result from the small mandible and a failure of lowering the tongue. Thus, our study identifies Rspo2 as a mesenchyme-derived factor that plays critical roles in regulating BA1 patterning and morphogenesis through ectodermal-mesenchymal interaction and a novel genetic factor for cleft palate.
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Registered trials
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