Homeobox protein notochord (NOTO) is atranscription factor[1] encoded by the gene notochord homeobox (NOTO) located on the short arm ofchromosome 2 (2p13.2) in humans (Homo sapiens).[2] Anortholog ofNOTO is found in the house mouse (Mus musculus), among other species, as the gene notochord homeobox (Noto) located on chromosome 6, which encodes thehomologous transcription factor homeobox protein notochord (Noto).[2]
In the house mouse, Noto is expressed in cells comprising theprimitive node (node) of the developing embryo and functions to define the shape of the primitive node, help develop the lateral (left-right) asymmetry of theembryo, and formcilia primarily onposterior nodal cells.[3] Noto is also essential for the proper development of thecaudalnotochord.[4]Noto acts downstream of the genesFoxa2 andT, and its expression is absent in embryos withmutant forms ofFoxa2 andT.[4] However, a direct relationship for the regulation ofNoto expression byFoxa2 andT has not yet been confirmed.[4] In contrast,Noto acts upstream ofFoxj1 andRfx3, which both function in theciliogenesis of certain other mouse tissues.[3]
Mouse embryos with mutant forms ofNoto have been characterized by shortened nodal cilia,basal bodies deeply embedded in the cellcytoplasm, and/or an abnormally-developed caudal notochord (complete absence in some cases).[5] In one experiment, replacingNoto withFoxj1 resulted in functional nodal cilia, but only withNoto expression were cilia localized on posterior nodal cells and the normal shape of the node established.[3] Additionally,Noto mutant embryos are subject to randomization of lateral asymmetry and are therefore often characterized by isomerization of the lungs, malformation of the cardiacoutflow tract,heterotaxia, and/orsitus inversus.[5]