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ZFIN ID: ZDB-PUB-061020-41
Sesn1 is a Novel Gene for Left-Right Asymmetry and Mediating Nodal Signaling
Peeters, H., Voz, M.L., Verschueren, K., De Cat, B., Pendeville, H., Thienpont, B., Schellens, A., Belmont, J.W., David, G., Van De Ven, W.J., Fryns, J.P., Gewillig, M., Huylebroeck, D., Peers, B., and Devriendt, K.
Date: 2006
Source: Human molecular genetics   15(22): 3369-3377 (Journal)
Registered Authors: De Cat, Bart, Peers, Bernard, Pendeville-Samain, Hélène, Voz, Marianne
Keywords: none
MeSH Terms:
  • Animals
  • Animals, Genetically Modified
  • Body Patterning/genetics*
  • Embryo, Nonmammalian/embryology
  • Embryo, Nonmammalian/metabolism
  • Forkhead Transcription Factors/genetics
  • Forkhead Transcription Factors/metabolism
  • Gene Expression
  • Gene Expression Regulation, Developmental*
  • Intracellular Signaling Peptides and Proteins/deficiency
  • Intracellular Signaling Peptides and Proteins/genetics
  • Intracellular Signaling Peptides and Proteins/metabolism*
  • Mutation/genetics
  • Nodal Protein
  • Protein Binding
  • Signal Transduction/genetics*
  • Transforming Growth Factor beta/metabolism*
  • Zebrafish/embryology*
  • Zebrafish/genetics*
  • Zebrafish/metabolism
  • Zebrafish Proteins/deficiency
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism*
PubMed: 17038485 Full text @ Hum. Mol. Genet.
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.