1. Asymmetric Nodal expression in the mouse is governed by the combinatorial activities of two distinct regulatory elements
- Author
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J. Ann Le Good, Elizabeth J. Robertson, Daniel B. Constam, Dominic P. Norris, Stéphane D. Vincent, and Harvard University Biological Laboratories
- Subjects
Embryology ,MESH: Integrases ,MESH: Gene Targeting ,Germline ,MESH: Genotype ,Mice ,0302 clinical medicine ,Transforming Growth Factor beta ,MESH: Gene Expression Regulation, Developmental ,MESH: Animals ,In Situ Hybridization ,Sequence Deletion ,MESH: Indoles ,Genetics ,0303 health sciences ,Chromosome Mapping ,Gene Expression Regulation, Developmental ,Embryo ,SUPERFAMILY ,MESH: Transcription Factors ,MESH: Crosses, Genetic ,Cell biology ,Enhancer Elements, Genetic ,MESH: Hepatocyte Nuclear Factor 4 ,Axis determination ,MESH: Mice, Transgenic ,Nodal Protein ,Molecular Sequence Data ,MESH: Gene Transfer Techniques ,Mice, Transgenic ,MESH: Histological Techniques ,Biology ,MESH: Phosphoproteins ,MESH: Digestive System ,03 medical and health sciences ,Animals ,MESH: Galactosides ,RNA, Messenger ,Enhancer ,MESH: Mice ,Alleles ,Body Patterning ,030304 developmental biology ,Base Sequence ,Lateral plate mesoderm ,[SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology ,MESH: Kidney ,Expression (computer science) ,Embryo, Mammalian ,MESH: Epithelium ,[SDV.GEN.GA]Life Sciences [q-bio]/Genetics/Animal genetics ,Viscera ,[SDV.BDD.EO]Life Sciences [q-bio]/Development Biology/Embryology and Organogenesis ,NODAL ,MESH: DNA-Binding Proteins ,030217 neurology & neurosurgery ,MESH: Liver ,Developmental Biology - Abstract
International audience; In all vertebrates, invariant left/right (L/R) positioning and organization of the internal viscera is controlled by a conserved pathway. Nodal, a member of the TGFbeta superfamily is a critical upstream component responsible for initiating L/R axis determination. Asymmetric Nodal expression in the node preceeds and foreshadows morphological L/R asymmetry. Here we address the mechanism of Nodal activation in the left LPM by studying the function of a novel enhancer element, the AIE. We show this element is exclusively active in cells of the left lateral plate mesoderm (LPM) and is not itself responding to Nodal asymmetry. To test the hypothesis that this element may initiate asymmetric Nodal expression in the LPM, we deleted it from the mouse germ line. Mice homozygous for the AIE deletion (Nodal(deltaaie/deltaaie)) show no defects. However, we find that the AIE contributes to regulating the level of asymmetric Nodal activity; analysis of transheterozygous embryos (Nodal(deltaaie/null)) shows reduced Nodal expression in the left LPM associated with a low penetrance of L/R defects. Our findings point to the existence of two independent pathways that control Nodal expression in the left LPM.
- Published
- 2004
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