Antagonizes the function of BMP4 by binding to it and preventing its interaction with receptors. Alters the fate commitment of neural stem cells from gliogenesis to neurogenesis. Contributes to neuronal differentiation of neural stem cells in the brain by preventing the adoption of a glial fate. May play a crucial role in dorsoventral axis formation. May play a role in embryonic bone formation (By similarity). May also play an important role in regulating retinal angiogenesis through modulation of BMP4 actions in endothelial cells. Plays a role during anterior segment eye development.
X-linked megalocornea (MGC1) is an ocular anterior segment disorder characterized by an increased cornea diameter and deep anterior chamber evident at birth and later onset of mosaic corneal degeneration (shagreen), arcus juvenilis, and presenile cataracts. We identified copy-number variation, frameshift, missense, splice-site and nonsense mutations in the Chordin-like 1 gene (CHRDL1) on Xq23 as the cause of the condition in seven MGC1 families. CHRDL1 encodes ventroptin, a bone morphogenic protein antagonist with a proposed role in specification of topographic retinotectal projections. Electrophysiological evaluation revealed mild generalized cone system dysfunction and, in one patient, an interhemispheric asymmetry in visual evoked potentials. We show that CHRDL1 is expressed in the developing human cornea and anterior segment in addition to the retina. We explored the impact of loss of ventroptin function on brain function and morphology in vivo. CHRDL1 is differentially expressed in the human fetal brain, and there is high expression in cerebellum and neocortex. We show that MGC1 patients have a superior cognitive ability despite a striking focal loss of myelination of white matter. Our findings reveal an unexpected requirement for ventroptin during anterior segment development and the consequences of a lack of function in the retina and brain.
PURPOSE: Pericytes play a specialized role in regulating angiogenesis and vascular function by providing vascular stability and controlling endothelial cell proliferation. Disorders in pericyte function and pericyte-endothelial interaction have been observed in several disease states including tumor angiogenesis and diabetic microangiopathy. In ischemic retinal disease, hypoxia is a potent driver of retinal angiogenesis. This study investigated the effects of hypoxia on retinal pericyte gene expression, and demonstrates a role in angiogenesis regulation for the hypoxia driven gene, chordin-like 1 (CHL-1). METHODS: In the current studies, we investigated hypoxia-induced gene expression in human retinal pericytes and found that expression of CHL-1, a member of the bone morphogenetic protein (BMP) superfamily, is upregulated by hypoxia. We investigated regulation of CHL-1 expression and the ability of CHL-1 to antagonize the antiangiogenic properties of BMP-4 using a human cell-based angiogenesis assay. RESULTS: We report that hypoxia induced hypoxia inducible factor-1alpha-driven expression of CHL-1. Both CHL-1 and BMP-4 were secreted from human retinal pericytes. We found that CHL-1 complexes with BMP-4 to antagonize the antiangiogenic effects of BMP-4, and that BMP-4 and vascular endothelial growth factor (VEGF) co-regulate angiogenesis. CONCLUSIONS: We propose that hypoxia-induced upregulation of CHL-1 alters the homeostatic balance between BMP-4 and VEGF to synergize with VEGF in driving retinal angiogenesis.
The process in which relatively unspecialized cells, e.g. embryonic or regenerative cells, acquire specialized structural and/or functional features that characterize the cells, tissues, or organs of the mature organism or some other relatively stable phase of the organism's life history. Differentiation includes the processes involved in commitment of a cell to a specific fate and its subsequent development to the mature state.
The process whose specific outcome is the progression of the compound eye over time, from its formation to the mature structure. The compound eye is an organ of sight that contains multiple repeating units, often arranged hexagonally. Each unit has its own lens and photoreceptor cell(s) and can generate either a single pixelated image or multiple images, per eye.
Evidence
1:
Inferred from Mutant PhenotypeUniProtKB
X-linked megalocornea (MGC1) is an ocular anterior segment disorder characterized by an increased cornea diameter and deep anterior chamber evident at birth and later onset of mosaic corneal degeneration (shagreen), arcus juvenilis, and presenile cataracts. We identified copy-number variation, frameshift, missense, splice-site and nonsense mutations in the Chordin-like 1 gene (CHRDL1) on Xq23 as the cause of the condition in seven MGC1 families. CHRDL1 encodes ventroptin, a bone morphogenic protein antagonist with a proposed role in specification of topographic retinotectal projections. Electrophysiological evaluation revealed mild generalized cone system dysfunction and, in one patient, an interhemispheric asymmetry in visual evoked potentials. We show that CHRDL1 is expressed in the developing human cornea and anterior segment in addition to the retina. We explored the impact of loss of ventroptin function on brain function and morphology in vivo. CHRDL1 is differentially expressed in the human fetal brain, and there is high expression in cerebellum and neocortex. We show that MGC1 patients have a superior cognitive ability despite a striking focal loss of myelination of white matter. Our findings reveal an unexpected requirement for ventroptin during anterior segment development and the consequences of a lack of function in the retina and brain.
X-linked megalocornea (MGC1) is an ocular anterior segment disorder characterized by an increased cornea diameter and deep anterior chamber evident at birth and later onset of mosaic corneal degeneration (shagreen), arcus juvenilis, and presenile cataracts. We identified copy-number variation, frameshift, missense, splice-site and nonsense mutations in the Chordin-like 1 gene (CHRDL1) on Xq23 as the cause of the condition in seven MGC1 families. CHRDL1 encodes ventroptin, a bone morphogenic protein antagonist with a proposed role in specification of topographic retinotectal projections. Electrophysiological evaluation revealed mild generalized cone system dysfunction and, in one patient, an interhemispheric asymmetry in visual evoked potentials. We show that CHRDL1 is expressed in the developing human cornea and anterior segment in addition to the retina. We explored the impact of loss of ventroptin function on brain function and morphology in vivo. CHRDL1 is differentially expressed in the human fetal brain, and there is high expression in cerebellum and neocortex. We show that MGC1 patients have a superior cognitive ability despite a striking focal loss of myelination of white matter. Our findings reveal an unexpected requirement for ventroptin during anterior segment development and the consequences of a lack of function in the retina and brain.
Protein involved in differentiation, the developmental process of a multicellular organism by which cells become specialized for particular functions. Differentiation requires selective expression of the genome; the fully differentiated state may be preceded by a stage in which the cell is already programmed for differentiation but is not yet expressing the characteristic phenotype determination. Also used for fungal conidiation proteins, and for some bacteria that present specialization of function in cell types, such as Caulobacter crescentus.
Protein involved in osteogenesis, the mechanism of bone formation wether intramembranous or endochondral. In intramembranous ossification, bone is formed by differentiation of mesenchymal cells into osteoblasts with absence of a cartilaginous model. The flat bones of the skull, the sternum, and the scapula are examples of bones that develop by intramembranous ossification. The term endochondral refers to the close association of the developing bone with the pre-existing hyaline cartilage model of that bone. The long bones of the limbs (including the phalanges) and the ribs develop by endochondral ossification.
Protein involved in development, the process whereby a multicellular organism develops from its early immature forms, e.g., zygote, larva, embryo, into an adult.
A reference proteome is a set of protein sequences derived from a complete proteome which constitutes a defined standard for a particular user community. Reference proteomes are manually defined according to a number of criteria. They cover the proteomes of well- studied model organisms and other proteomes of interest for biomedical and biotechnological research. Reference proteomes have been selected to provide broad coverage of the tree of life, and constitute a representative cross-section of the taxonomic diversity to be found within UniProtKB.
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