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Two additional midline barriers function with midline lefty1 expression to maintain asymmetric Nodal signaling during left-right axis specification in zebrafish.

Left-right (L/R) patterning is crucial for the proper development of all vertebrates and requires asymmetric expression of nodal in the lateral plate mesoderm (LPM). The mechanisms governing asymmetric initiation of nodal have been studied extensively, but because Nodal is a potent activator of its own transcription, it is also crucial to understand the regulation required to maintain this asymmetry once it is established. The 'midline barrier', consisting of lefty1 expression, is a conserved mechanism for restricting Nodal activity to the left. However, the anterior and posterior extremes of the LPM are competent to respond to Nodal signals yet are not adjacent to this barrier, suggesting that lefty1 is not the only mechanism preventing ectopic Nodal activation. Here, we demonstrate the existence of two additional midline barriers. The first is a 'posterior barrier' mediated by Bmp signaling that prevents nodal propagation through the posterior LPM. In contrast to previous reports, we find that Bmp represses Nodal signaling independently of lefty1 expression and through the activity of a ligand other than Bmp4. The 'anterior barrier' is mediated by lefty2 expression in the left cardiac field and prevents Nodal activation from traveling across the anterior limit of the notochord and propagating down the right LPM. Both barriers appear to be conserved across model systems and are thus likely to be present in all vertebrates.

Pubmed ID: 21937597

Authors

  • Lenhart KF
  • Lin SY
  • Titus TA
  • Postlethwait JH
  • Burdine RD

Journal

Development (Cambridge, England)

Publication Data

October 22, 2011

Associated Grants

  • Agency: NICHD NIH HHS, Id: P01 HD022486
  • Agency: NICHD NIH HHS, Id: P01HD022486
  • Agency: NICHD NIH HHS, Id: R01 HD048584
  • Agency: NICHD NIH HHS, Id: R01 HD048584
  • Agency: NHGRI NIH HHS, Id: R01 HG002995

Mesh Terms

  • Activin Receptors, Type I
  • Animals
  • Base Sequence
  • Body Patterning
  • Bone Morphogenetic Protein 4
  • Bone Morphogenetic Proteins
  • DNA Primers
  • Gene Expression Regulation, Developmental
  • Heart
  • Left-Right Determination Factors
  • Ligands
  • Mesoderm
  • Models, Biological
  • Mutation
  • Nodal Protein
  • Notochord
  • Signal Transduction
  • Zebrafish
  • Zebrafish Proteins