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 and Rebecca D. Burdine
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.
Two additional midline barriers function with midline lefty1 expression to maintain asymmetric Nodal signaling during left-right axis specification in zebrafish
Creators
Kari F. Lenhart - Princeton University
Shin-Yi Lin - Princeton University
Tom A. Titus - University of Oregon
John H. Postlethwait - University of Oregon
Rebecca D. Burdine - Princeton University
Publication Details
Development (Cambridge), v 138(20), pp 4405-4410
Publisher
Company of Biologists
Resource Type
Journal article
Language
English
Academic Unit
Biology
Web of Science ID
WOS:000295085600008
Scopus ID
2-s2.0-80053071525
Other Identifier
991020100074704721
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