Cell adhesion molecule-related/down-regulated by oncogenes is a

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme catalysis, catalysing metab ...

that in humans is encoded by the ''CDON''

gene In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei ...

. CDON and BOC are cell surface receptors of the immunoglobulin (Ig)/fibronectin type III (

FNIII The Fibronectin type III domain is an evolutionarily conserved protein domain that is widely found in animal proteins. The fibronectin protein in which this domain was first identified contains 16 copies of this domain. The domain is about 100 am ...

) repeat family involved in myogenic differentiation. CDON and BOC are coexpressed during development, form complexes with each other in a cis fashion, and are related to each other in their

ectodomain An ectodomain is the domain of a membrane protein that extends into the extracellular space (the space outside a cell). Ectodomains are usually the parts of proteins that initiate contact with surfaces, which leads to signal transduction. A n ...

s, but each has a unique long cytoplasmic tail.

Structure and function

Cell adhesion molecule-related/down-regulated by oncogenes (CDON) is a conserved transmembrane

glycoprotein Glycoproteins are proteins which contain oligosaccharide (sugar) chains covalently attached to amino acid side-chains. The carbohydrate is attached to the protein in a cotranslational or posttranslational modification. This process is known a ...

belonging to a subgroup of the

immunoglobulin superfamily The immunoglobulin superfamily (IgSF) is a large protein superfamily of cell surface and soluble proteins that are involved in the recognition, binding, or adhesion processes of cells. Molecules are categorized as members of this superfamily ...

cell adhesion molecule Cell adhesion molecules (CAMs) are a subset of cell surface proteins that are involved in the binding of cells with other cells or with the extracellular matrix (ECM), in a process called cell adhesion. In essence, CAMs help cells stick to each ...

s. It is highly expressed in both the

somite The somites (outdated term: primitive segments) are a set of bilaterally paired blocks of paraxial mesoderm that form in the embryogenesis, embryonic stage of somitogenesis, along the head-to-tail axis in segmentation (biology), segmented animals. ...

s and dorsal lips of the

neural tube In the developing chordate (including vertebrates), the neural tube is the embryonic precursor to the central nervous system, which is made up of the brain and spinal cord. The neural groove gradually deepens as the neural folds become elevated, ...

of embryonic day 8.5 mice. It is expressed in proliferating and differentiating

myoblast Myogenesis is the formation of skeletal muscular tissue, particularly during embryonic development. Muscle fibers generally form through the fusion of precursor myoblasts into multinucleated fibers called myotubes. In the early development o ...

cell lines, there is evidence showing its role in mediating the effects of cell–cell interactions between muscle precursors that are critical in

myogenesis Myogenesis is the formation of skeletal muscle, skeletal muscular tissue, particularly during embryonic development. Skeletal muscle#Skeletal muscle cells, Muscle fibers generally form through the fusion of precursor cell, precursor myoblasts in ...

. It is also expressed in

neural crest The neural crest is a ridge-like structure that is formed transiently between the epidermal ectoderm and neural plate during vertebrate development. Neural crest cells originate from this structure through the epithelial-mesenchymal transition, ...

precursor cells, it regulates the localization of

N-cadherin Cadherin-2 also known as Neural cadherin (N-cadherin), is a protein that in humans is encoded by the ''CDH2'' gene. CDH2 has also been designated as CD325 (cluster of differentiation 325). Cadherin-2 is a transmembrane protein expressed in multi ...

providing a mechanism for directed neural crest migration. CDON protein was shown to bind to all three mammalian isoforms of hedgehog proteins: Sonic Hh, Indian Hh, and Desert Hh.

Clinical significance

CDON mutations are thought to diminish

sonic hedgehog Sonic hedgehog protein (SHH) is a major signaling molecule of embryonic development in humans and animals, encoded by the ''SHH'' gene. This signaling molecule is key in regulating embryonic morphogenesis in all animals. SHH controls organoge ...

(SHH)-pathway activity which is important in stimulating cell proliferation, differentiation, and tissue patterning at multiple points in animal development. CDON was shown to play a role in differentiation of midbrain dopaminergic neurons through the interference with of Shh signaling pathway. Mutations in CDON gene has been associated with

Holoprosencephaly Holoprosencephaly (HPE) is a cephalic disorder in which the prosencephalon (the forebrain of the embryo) fails to Prenatal development, develop into two Cerebral hemisphere, hemispheres, typically occurring between the 18th and 28th day of gestati ...

which is structural anomaly of the brain, in which the developing forebrain fails to correctly separate into right and left hemispheres. CDON mutations synergistically interact with prenatal alcohol exposure to increase susceptibility to Holoprosencephaly.

Gene knockdown studies

CDON knockdown using

morpholino A Morpholino, also known as a Morpholino oligomer and as a phosphorodiamidate Morpholino oligomer (PMO), is a type of oligomer molecule (colloquially, an oligo) used in molecular biology to modify gene expression. Its molecular structure contains ...

s in zebra fish altered the eye development, CDON was shown important in restraining the size of the optic stalk and ventral retina in chick embryos. Additionally, double CDON knock out mice display

optic nerve hypoplasia Optic nerve hypoplasia (ONH) is a medical condition arising from the underdevelopment (hypoplasia) of the optic nerve(s). This condition is the most common congenital optic nerve anomaly. The optic disc appears abnormally small because not all t ...

(ONH), a prominent feature of

septo-optic dysplasia Septo-optic dysplasia (SOD), known also as de Morsier syndrome, is a rare congenital malformation syndrome that features a combination of the underdevelopment of the optic nerve, pituitary gland dysfunction, and absence of the septum pellucidum (a ...

(SOD), the same phenotype shown by treating mice prenatally with ethanol. CDON^−/− animals also show cardiac dysfunction with increased

fibrosis Fibrosis, also known as fibrotic scarring, is the development of fibrous connective tissue in response to an injury. Fibrosis can be a normal connective tissue deposition or excessive tissue deposition caused by a disease. Repeated injuries, ch ...

, those cardiac effects are mediated through hyperactivation of WNT/β-catenin signaling.

Interactions

CDON has been shown to

interact Advocates for Informed Choice, dba interACT or interACT Advocates for Intersex Youth, is a 501(c)(3) nonprofit organization advocating for the legal and human rights of children with intersex traits. The organization was founded in 2006 and fo ...

with CDH1 and BOC.

References

External links