View source for Notochord homeobox (NOTO) gene

'''Homeobox protein notochord (NOTO)''' is a [[transcription factor]]<ref name="ref1">The UniProt Consortium; UniProt: the universal protein knowledgebase. ''Nucleic Acids Res'' 2017; 45 (D1): D158-D169. doi: 10.1093/nar/gkw1099.</ref> encoded by the gene notochord homeobox (''NOTO'') located on the short arm of [[chromosome]] 2 (2p13.2) in humans (''[[Homo sapiens]]'').<ref name="ref2">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.</ref> An [[ortholog]] of ''NOTO'' is found in the house mouse (''[[Mus musculus]]''), among other species, as the gene notochord homeobox (''Noto'') located on chromosome 6, which encodes the [[Sequence homology|homologous]] transcription factor homeobox protein notochord (Noto).<ref name="ref2"/>

In the house mouse, Noto is expressed in cells comprising the [[primitive node]] (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]], and form [[cilia]] primarily on [[posterior (anatomy)|posterior]] nodal cells.<ref name="ref3">Alten, Leonie, et al. "Differential regulation of node formation, nodal ciliogenesis and cilia positioning by Noto and Foxj1." ''Development'' 139.7 (2012): 1276-1284.</ref> Noto is also essential for the proper development of the [[caudal (anatomical term)|caudal]] [[notochord]].<ref name="ref4">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.</ref> ''Noto'' acts downstream of the genes ''Foxa2'' and ''T'', and its expression is absent in embryos with [[mutant]] forms of ''Foxa2'' and ''T''.<ref name="ref4"/> However, a direct relationship for the regulation of ''Noto'' expression by ''Foxa2'' and ''T'' has not yet been confirmed.<ref name="ref4"/> In contrast, ''Noto'' acts upstream of ''Foxj1'' and ''Rfx3'', which both function in the [[ciliogenesis]] of certain other mouse tissues.<ref name="ref3"/>

Mouse embryos with mutant forms of ''Noto'' have been characterized by shortened nodal cilia, [[basal bodies]] deeply embedded in the cell [[cytoplasm]], and/or an abnormally-developed caudal notochord (complete absence in some cases).<ref name="ref5">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.</ref> 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.<ref name="ref3"/> 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 [[Ventricular outflow tract|outflow tract]], [[heterotaxia]], and/or [[situs inversus]].<ref name="ref5"/> 

== References ==
{{reflist}}

[[Category:Genes on human chromosome 2]]