ABSTRACT
The role of Lefty2 in left-right patterning was investigated by analysis of mutant mice that lack asymmetric expression of lefty2. These animals exhibited various situs defects including left isomerism. The asymmetric expression of nodal was prolonged and the expression of Pitx2 was upregulated in the mutant embryos. The absence of Lefty2 conferred on Nodal the ability to diffuse over a long distance. Thus, Nodal-responsive genes, including Pitx2, that are normally expressed on the left side were expressed bilaterally in the mutant embryos, even though nodal expression was confined to the left side. These results suggest that Nodal is a long-range signaling molecule but that its range of action is normally limited by the feedback inhibitor Lefty2.
Subject(s)
Body Patterning/physiology , Nuclear Proteins , Transforming Growth Factor beta/genetics , Transforming Growth Factor beta/metabolism , Animals , DNA-Binding Proteins/metabolism , Diffusion , Feedback, Physiological/physiology , Gene Deletion , Gene Expression Regulation, Developmental , Homeodomain Proteins/genetics , Left-Right Determination Factors , Mice , Mice, Inbred C57BL , Mice, Knockout , Nodal Protein , Phosphorylation , Signal Transduction/physiology , Smad2 Protein , Trans-Activators/metabolism , Transcription Factors/genetics , Homeobox Protein PITX2ABSTRACT
Dorsal and ventral aspects of the eye are distinct from the early stages of development. The developing eye cup grows dorsally, and the choroidal fissure is formed on its ventral side. Retinal axons from the dorsal and ventral retina project to the ventral and dorsal tectum, respectively. Misexpression of the Tbx5 gene induced dorsalization of the ventral side of the eye and altered projections of retinal ganglion cell axons. Thus, Tbx5 is involved in eye morphogenesis and is a topographic determinant of the visual projections between retina and tectum.
Subject(s)
Avian Proteins , Axons/ultrastructure , Eye/embryology , Retina/embryology , Superior Colliculi/embryology , T-Box Domain Proteins/physiology , Animals , Body Patterning , Bone Morphogenetic Protein 4 , Bone Morphogenetic Proteins/genetics , Bone Morphogenetic Proteins/physiology , Chick Embryo , DNA-Binding Proteins/genetics , Electroporation , Ephrin-B1 , Ephrin-B2 , Gene Expression , Homeodomain Proteins/genetics , Membrane Proteins/genetics , Membrane Proteins/physiology , Morphogenesis , PAX2 Transcription Factor , Pigment Epithelium of Eye/embryology , Pigment Epithelium of Eye/metabolism , Retina/metabolism , Retinal Ganglion Cells/ultrastructure , T-Box Domain Proteins/genetics , Transcription Factors/genetics , Transfection , TransgenesABSTRACT
Much progress has been made in understanding limb development. Most genes are expressed equally and in the same pattern in the fore- and hindlimbs, which nevertheless develop into distinct structures. The T-box genes Tbx5 and Tbx4, on the other hand, are expressed differently in chick wing (Tbx5) and leg (Tbx4) buds. Molecular analysis of the optomotor blind gene, which belongs to the same family of transcription factors, has revealed that this gene is involved in the transdetermination of Drosophila wing and leg imaginal discs. In addition, expression of Tbx5 and Tbx4 correlates well with the identity of ectopic limb buds induced by fibroblast growth factor. Thus, it is thought that Tbx5 and Tbx4 might be involved in determining limb identity. Another candidate is the Pitx1 gene, which encodes a bicoid-type homeodomain transcription factor that is expressed in leg buds. Here we determine the importance of these factors in establishing limb identity.
