Sesn1 is a novel gene for left-right asymmetry and mediating nodal signaling
| Autor: | Willem Van de Ven, Marc Gewillig, Hilde Peeters, Kristin Verschueren, Danny Huylebroeck, Ann Schellens, Hélène Pendeville, John W. Belmont, Jean-Pierre Fryns, Marianne Voz, Koenraad Devriendt, Bernard Peers, Bernard Thienpont, Guido David, Bart De Cat |
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| Rok vydání: | 2006 |
| Předmět: |
Candidate gene
Embryo Nonmammalian Positional cloning Nodal Protein Nodal signaling Gene Expression Animals Genetically Modified Transforming Growth Factor beta Bone plate Genetics Animals Molecular Biology Zebrafish Genetics (clinical) Body Patterning Regulation of gene expression biology Lateral plate mesoderm Intracellular Signaling Peptides and Proteins Gene Expression Regulation Developmental Lefty Forkhead Transcription Factors General Medicine Zebrafish Proteins biology.organism_classification Cell biology Mutation Protein Binding Signal Transduction |
| Zdroj: | Human molecular genetics. 15(22) |
| ISSN: | 0964-6906 |
| Popis: | Remarkable progress has been made in understanding the molecular mechanisms underlying left-right asymmetry in vertebrate animal models but little is known on left-right axis formation in humans. Previously, we identified SESN1 (also known as PA26) as a candidate gene for heterotaxia by positional cloning of the breakpoint regions of a de novo translocation in a heterotaxia patient. In this study, we show by means of a zebrafish sesn1-knockdown model that Sesn1 is required for normal embryonic left-right determination. In this model, developmental defects and expression data of genes implicated in vertebrate left-right asymmetry indicate a role for Sesn1 in mediating Nodal signaling. In the lateral plate mesoderm, Nodal signaling plays a central role in left-right axis formation in vertebrates and is mediated by FoxH1 transcriptional induction. In line with this, we show that Sesn1 physically interacts with FoxH1 or a FoxH1-containing complex. Mutation analysis in a panel of 234 patients with isolated heterotaxia did not reveal mutations, indicating that these are only exceptional causes of human heterotaxia. In this study, we identify SESN1 as an indispensable gene for vertebrate left-right asymmetry and a new player in mediating Nodal signaling. |
| Databáze: | OpenAIRE |
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