ArticleInvestigative ophthalmology & visual science2008
Functions of the type 1 BMP receptor Acvr1 (Alk2) in lens development: cell proliferation, terminal differentiation, and survival.
Article in Investigative ophthalmology & visual science, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 45 citations in OpenAlex.
- ABCC6 Involvement in Cerebral Small Vessel Disease: Potential Mechanisms and Associations.Genes · 2025Review
- Protective Effect and Mechanism of Bone Morphogenetic Protein-4 on Apoptosis of Human Lens Epithelium Cells under Oxidative Stress.BioMed research international · 2021Article
- Transcriptomic analysis and novel insights into lens fibre cell differentiation regulated by Gata3.Open biology · 2019Article
- ACVR1 Function in Health and Disease.Cells · 2019Review
- Pathogenic variants in the ABCC6 gene are associated with an increased risk for ischemic stroke.Brain pathology (Zurich, Switzerland) · 2018Article
- Endogenous bioelectric currents promote differentiation of the mammalian lens.Journal of cellular physiology · 2018Article
- Animal models of fibrodysplasia ossificans progressiva.Developmental dynamics : an official publication of the American Association of Anatomists · 2018Review
- Embryonic Surface Ectoderm-specific Mitofusin 2 Conditional Knockout Induces Congenital Cataracts in Mice.Scientific reports · 2018Article
- TGF-β Family Signaling in Epithelial Differentiation and Epithelial-Mesenchymal Transition.Cold Spring Harbor perspectives in biology · 2018Review
- Signaling and Gene Regulatory Networks in Mammalian Lens Development.Trends in genetics : TIG · 2017Review
- Systems biology of lens development: A paradigm for disease gene discovery in the eye.Experimental eye research · 2017Review
- Common mutations in ALK2/ACVR1, a multi-faceted receptor, have roles in distinct pediatric musculoskeletal and neural orphan disorders.Cytokine & growth factor reviews · 2016Review
- Anterior segment dysgenesis correlation with epithelial-mesenchymal transition in Smad4 knockout mice.International journal of ophthalmology · 2016Article
- Bone Morphogenetic Protein (BMP) signaling in development and human diseases.Genes & diseases · 2014Article
- Interactions between lens epithelial and fiber cells reveal an intrinsic self-assembly mechanism.Developmental biology · 2014Article
- c-Myc regulates cell proliferation during lens development.PloS one · 2014Article
- Identification and characterization of FGF2-dependent mRNA: microRNA networks during lens fiber cell differentiation.G3 (Bethesda, Md.) · 2013Article
- Patterns of gene expression in microarrays and expressed sequence tags from normal and cataractous lenses.Human genomics · 2012Article
- Loss of Msx2 function down-regulates the FoxE3 expression and results in anterior segment dysgenesis resembling Peters anomaly.The American journal of pathology · 2012Article
- Abcc6 deficiency causes increased infarct size and apoptosis in a mouse cardiac ischemia-reperfusion model.Arteriosclerosis, thrombosis, and vascular biology · 2011Article
Corrections and comments
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Authors and funding
9 authors at 5 institutions in 2 countries.
Funding
Abstract
purposeBone morphogenetic protein (BMP) signaling is essential for the induction and subsequent development of the lens. The purpose of this study was to analyze the function(s) of the type 1 BMP receptor, Acvr1, in lens development.
methodsAcvr1 was deleted from the surface ectoderm of mouse embryos on embryonic day 9 using the Cre-loxP
methodCell proliferation, cell cycle exit, and apoptosis were measured in tissue sections by immunohistochemistry, immunofluorescence, and TUNEL staining.
resultsLenses formed in the absence of Acvr1. However, Acvr1(CKO) (conditional knockout) lenses were small. Acvr1 signaling promoted proliferation at early stages of lens formation but inhibited proliferation at later stages. Inhibition of cell proliferation by Acvr1 was necessary for the proper regionalization of the lens epithelium and promoted the withdrawal of lens fiber cells from the cell cycle. In spite of the failure of all Acvr1(CKO) fiber cells to withdraw from the cell cycle, they expressed proteins characteristic of differentiated fiber cells. Although the stimulation of proliferation was Smad independent, the ability of Acvr1 to promote cell cycle exit later in development depended on classical R-Smad-Smad4 signaling. Loss of Acvr1 led to an increase in apoptosis of lens epithelial and fiber cells. Increased cell death, together with the initial decrease in proliferation, appeared to account for the smaller sizes of the Acvr1(CKO) lenses.
conclusionsThis study revealed a novel switch in the functions of Acvr1 in regulating lens cell proliferation. Previously unknown functions mediated by this receptor included regionalization of the lens epithelium and cell cycle exit during fiber cell differentiation.
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