NODAL
Encyclopedia
Nodal is a protein
that in humans is encoded by the NODAL gene
. It is a member of the TGF beta
superfamily. Like many other members of this superfamily, it is involved in cell differentiation. Studies of the mouse counterpart suggested that this gene may be essential for mesoderm
formation and subsequent organization of left-right axial structures in early embryonic development.
s is established by a process that uses the Nodal and Lefty
proteins; Nodal is expressed in the left side of the organism in early development. An ortholog of Nodal was recently found in snail
s and was shown to be involved in left-right asymmetry as well.
Nodal signaling is important very early in development
for cell fate determination and for many other developmental processes. A nodal knockout in mouse
causes the absence of the primitive streak and failure in the formation of mesoderm
, leading to developmental arrest just after gastrulation
.
Nodal is widely distributed cytokine
. The presence of Nodal is not only limited to vertebrates, it is also known to be conserved in other chordate
s, deuterostome
s (cephalochordates, tunicate
s and echinoderm
s) and protostome
s such as snails, but interestingly neither the nematode C. elegans (another protosome) nor the fruit fly (an arthropode) have a copy of nodal. Although mouse and human only have one nodal gene, the zebra fish contain three nodal paralogs: squint , cyclops and southpaw, and the frog five (xnr1,2,3,5 and 6). Even though the zebra fish Nodal homologs are very similar, they have specialized to perform different roles; for instance, Squint and Cyclops are important for mesoendoderm formation, whereas to Southpaw that has a major role in asymmetric heart morphogenesis
and visceral left-right asymmetry. Another example of protein speciation is the case of the frog where Xnr1 and Xnr2 regulate movements in gastrulation in contrast to Xnr5 and Xnr6 that are involved in mesoderm induction. Mouse Nodal has been implicated in left-right asymmetry, neural pattering and mesoderm induction (see nodal signaling
).
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
that in humans is encoded by the NODAL gene
Gene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...
. It is a member of the TGF beta
Transforming growth factor beta superfamily
The transforming growth factor beta superfamily is a large family of structurally related cell regulatory proteins that was named after its first member, TGF-β1, originally described in 1983....
superfamily. Like many other members of this superfamily, it is involved in cell differentiation. Studies of the mouse counterpart suggested that this gene may be essential for mesoderm
Mesoderm
In all bilaterian animals, the mesoderm is one of the three primary germ cell layers in the very early embryo. The other two layers are the ectoderm and endoderm , with the mesoderm as the middle layer between them.The mesoderm forms mesenchyme , mesothelium, non-epithelial blood corpuscles and...
formation and subsequent organization of left-right axial structures in early embryonic development.
Function
The left-right asymmetry in the body of vertebrateVertebrate
Vertebrates are animals that are members of the subphylum Vertebrata . Vertebrates are the largest group of chordates, with currently about 58,000 species described. Vertebrates include the jawless fishes, bony fishes, sharks and rays, amphibians, reptiles, mammals, and birds...
s is established by a process that uses the Nodal and Lefty
Lefty (protein)
Lefty are proteins that are closely related members of the TGF-beta family of growth factors. These proteins are secreted and play a role in left-right asymmetry determination of organ systems during development...
proteins; Nodal is expressed in the left side of the organism in early development. An ortholog of Nodal was recently found in snail
Snail
Snail is a common name applied to most of the members of the molluscan class Gastropoda that have coiled shells in the adult stage. When the word is used in its most general sense, it includes sea snails, land snails and freshwater snails. The word snail without any qualifier is however more often...
s and was shown to be involved in left-right asymmetry as well.
Nodal signaling is important very early in development
Developmental biology
Developmental biology is the study of the process by which organisms grow and develop. Modern developmental biology studies the genetic control of cell growth, differentiation and "morphogenesis", which is the process that gives rise to tissues, organs and anatomy.- Related fields of study...
for cell fate determination and for many other developmental processes. A nodal knockout in mouse
Mouse
A mouse is a small mammal belonging to the order of rodents. The best known mouse species is the common house mouse . It is also a popular pet. In some places, certain kinds of field mice are also common. This rodent is eaten by large birds such as hawks and eagles...
causes the absence of the primitive streak and failure in the formation of mesoderm
Mesoderm
In all bilaterian animals, the mesoderm is one of the three primary germ cell layers in the very early embryo. The other two layers are the ectoderm and endoderm , with the mesoderm as the middle layer between them.The mesoderm forms mesenchyme , mesothelium, non-epithelial blood corpuscles and...
, leading to developmental arrest just after gastrulation
Gastrulation
Gastrulation is a phase early in the embryonic development of most animals, during which the single-layered blastula is reorganized into a trilaminar structure known as the gastrula. These three germ layers are known as the ectoderm, mesoderm, and endoderm.Gastrulation takes place after cleavage...
.
Nodal is widely distributed cytokine
Cytokine
Cytokines are small cell-signaling protein molecules that are secreted by the glial cells of the nervous system and by numerous cells of the immune system and are a category of signaling molecules used extensively in intercellular communication...
. The presence of Nodal is not only limited to vertebrates, it is also known to be conserved in other chordate
Chordate
Chordates are animals which are either vertebrates or one of several closely related invertebrates. They are united by having, for at least some period of their life cycle, a notochord, a hollow dorsal nerve cord, pharyngeal slits, an endostyle, and a post-anal tail...
s, deuterostome
Deuterostome
Deuterostomes are a superphylum of animals. They are a subtaxon of the Bilateria branch of the subregnum Eumetazoa, and are opposed to the protostomes...
s (cephalochordates, tunicate
Tunicate
Tunicates, also known as urochordates, are members of the subphylum Tunicata, previously known as Urochordata, a group of underwater saclike filter feeders with incurrent and excurrent siphons that is classified within the phylum Chordata. While most tunicates live on the ocean floor, others such...
s and echinoderm
Echinoderm
Echinoderms are a phylum of marine animals. Echinoderms are found at every ocean depth, from the intertidal zone to the abyssal zone....
s) and protostome
Protostome
Protostomia are a clade of animals. Together with the deuterostomes and a few smaller phyla, they make up the Bilateria, mostly comprising animals with bilateral symmetry and three germ layers...
s such as snails, but interestingly neither the nematode C. elegans (another protosome) nor the fruit fly (an arthropode) have a copy of nodal. Although mouse and human only have one nodal gene, the zebra fish contain three nodal paralogs: squint , cyclops and southpaw, and the frog five (xnr1,2,3,5 and 6). Even though the zebra fish Nodal homologs are very similar, they have specialized to perform different roles; for instance, Squint and Cyclops are important for mesoendoderm formation, whereas to Southpaw that has a major role in asymmetric heart morphogenesis
Morphogenesis
Morphogenesis , is the biological process that causes an organism to develop its shape...
and visceral left-right asymmetry. Another example of protein speciation is the case of the frog where Xnr1 and Xnr2 regulate movements in gastrulation in contrast to Xnr5 and Xnr6 that are involved in mesoderm induction. Mouse Nodal has been implicated in left-right asymmetry, neural pattering and mesoderm induction (see nodal signaling
Nodal signaling
Nodal signaling is a signal transduction pathway that is important in pattern formation and differentiation during embryo development.The nodal family of proteins, a subset of the transforming growth factor beta superfamily, is responsible for mesoendoderm induction, patterning of the nervous...
).