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

Kari F. Lenhart, Shin Yi Lin, Tom A. Titus, John H. Postlethwait, Rebecca D. Burdine

    Research output: Contribution to journalArticlepeer-review

    31 Scopus citations

    Abstract

    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.

    Original languageEnglish (US)
    Pages (from-to)4405-4410
    Number of pages6
    JournalDevelopment
    Volume138
    Issue number20
    DOIs
    StatePublished - Oct 15 2011

    All Science Journal Classification (ASJC) codes

    • Molecular Biology
    • Developmental Biology

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