Homeobox protein notochord (NOTO) is a

transcription factor In molecular biology, a transcription factor (TF) (or sequence-specific DNA-binding factor) is a protein that controls the rate of transcription of genetic information from DNA to messenger RNA, by binding to a specific DNA sequence. The fu ...

The UniProt Consortium; UniProt: the universal protein knowledgebase. ''Nucleic Acids Res'' 2017; 45 (D1): D158-D169. doi: 10.1093/nar/gkw1099. encoded by the gene notochord homeobox (''NOTO'') located on the short arm of

chromosome A chromosome is a long DNA molecule with part or all of the genetic material of an organism. In most chromosomes the very long thin DNA fibers are coated with packaging proteins; in eukaryotic cells the most important of these proteins are ...

2 (2p13.2) in humans (''

Homo sapiens Humans (''Homo sapiens'') are the most abundant and widespread species of primate, characterized by bipedalism and exceptional cognitive skills due to a large and complex brain. This has enabled the development of advanced tools, culture, ...

'').NCBI Resource Coordinators. Database resources of the National Center for Biotechnology Information. ''Nucleic Acids Research''. 2016;44(Database issue):D7-D19. doi:10.1093/nar/gkv1290. An

ortholog Sequence homology is the biological homology between DNA, RNA, or protein sequences, defined in terms of shared ancestry in the evolutionary history of life. Two segments of DNA can have shared ancestry because of three phenomena: either a spec ...

of ''NOTO'' is found in the house mouse (''

Mus musculus Mus or MUS may refer to: Abbreviations * MUS, the NATO country code for Mauritius * MUS, the IATA airport code for Minami Torishima Airport * MUS, abbreviation for the Centre for Modern Urban Studies on Campus The Hague, Leiden University, Neth ...

''), among other species, as the gene notochord homeobox (''Noto'') located on chromosome 6, which encodes the homologous transcription factor homeobox protein notochord (Noto). In the house mouse, Noto is expressed in cells comprising the

primitive node The primitive node (or primitive knot) is the organizer for gastrulation in most amniote embryos. In birds it is known as Hensen's node, and in amphibians it is known as the Spemann-Mangold organizer. It is induced by the Nieuwkoop center in am ...

(node) of the developing embryo and functions to define the shape of the primitive node, help develop the lateral (left-right) asymmetry of the

embryo An embryo is an initial stage of development of a multicellular organism. In organisms that reproduce sexually, embryonic development is the part of the life cycle that begins just after fertilization of the female egg cell by the male spe ...

, and form

cilia The cilium, plural cilia (), is a membrane-bound organelle found on most types of eukaryotic cell, and certain microorganisms known as ciliates. Cilia are absent in bacteria and archaea. The cilium has the shape of a slender threadlike projecti ...

primarily on posterior nodal cells.Alten, Leonie, et al. "Differential regulation of node formation, nodal ciliogenesis and cilia positioning by Noto and Foxj1." ''Development'' 139.7 (2012): 1276-1284. Noto is also essential for the proper development of the caudal

notochord In anatomy, the notochord is a flexible rod which is similar in structure to the stiffer cartilage. If a species has a notochord at any stage of its life cycle (along with 4 other features), it is, by definition, a chordate. The notochord consis ...

.Abdelkhalek, Hanaa Ben, et al. "The mouse homeobox gene Not is required for caudal notochord development and affected by the truncate mutation." ''Genes & development'' 18.14 (2004): 1725-1736. ''Noto'' acts downstream of the genes ''Foxa2'' and ''T'', and its expression is absent in embryos with

mutant In biology, and especially in genetics, a mutant is an organism or a new genetic character arising or resulting from an instance of mutation, which is generally an alteration of the DNA sequence of the genome or chromosome of an organism. It ...

forms of ''Foxa2'' and ''T''. However, a direct relationship for the regulation of ''Noto'' expression by ''Foxa2'' and ''T'' has not yet been confirmed. In contrast, ''Noto'' acts upstream of ''Foxj1'' and ''Rfx3'', which both function in the

ciliogenesis Ciliogenesis is defined as the building of the cell's antenna (primary cilia) or extracellular fluid mediation mechanism (motile cilium). It includes the assembly and disassembly of the cilia during the cell cycle. Cilia are important organelles ...

of certain other mouse tissues. Mouse embryos with mutant forms of ''Noto'' have been characterized by shortened nodal cilia,

basal bodies A basal body (synonymous with basal granule, kinetosome, and in older cytological literature with blepharoplast) is a protein structure found at the base of a eukaryotic undulipodium (cilium or flagellum). The basal body was named by Theodor W ...

deeply embedded in the cell

cytoplasm In cell biology, the cytoplasm is all of the material within a eukaryotic cell, enclosed by the cell membrane, except for the cell nucleus. The material inside the nucleus and contained within the nuclear membrane is termed the nucleoplasm. The ...

, and/or an abnormally-developed caudal notochord (complete absence in some cases).Beckers, Anja, et al. "The mouse homeobox gene Noto regulates node morphogenesis, notochordal ciliogenesis, and left-right patterning." ''Proceedings of the National Academy of Sciences'' 104.40 (2007): 15765-15770. In one experiment, replacing ''Noto'' with ''Foxj1'' resulted in functional nodal cilia, but only with ''Noto'' expression were cilia localized on posterior nodal cells and the normal shape of the node established. Additionally, ''Noto'' mutant embryos are subject to randomization of lateral asymmetry and are therefore often characterized by isomerization of the lungs, malformation of the cardiac outflow tract,

heterotaxia Situs ambiguus is a rare congenital defect in which the major visceral organs are distributed abnormally within the chest and abdomen. Clinically heterotaxy spectrum generally refers to any defect of Left-right asymmetry and arrangement of the vi ...

, and/or

situs inversus Situs inversus (also called situs transversus or oppositus) is a congenital condition in which the major visceral organs are reversed or mirrored from their normal positions. The normal arrangement of internal organs is known as situs solitus. Al ...

References

{{reflist Genes on human chromosome 2